Breastfeeding in Mothers of Preterm Infants

Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1398

Breastfeeding in mothers of preterm infants

Prevalence and effects of support

JENNY ERICSON

ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-513-0161-7 UPPSALA urn:nbn:se:uu:diva-333575 2018 Dissertation presented at Uppsala University to be publicly examined in Föreläsningssalen, Falu lasarett, Falun, Thursday, 18 January 2018 at 09:00 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in Swedish. Faculty examiner: Docent Helena Wigert (Göteborgs Universitet).

Abstract Ericson, J. 2018. Breastfeeding in mothers of preterm infants. Prevalence and effects of support. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1398. 69 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-513-0161-7.

The overall aim of this thesis was to describe the prevalence of breastfeeding in preterm infants and to evaluate the effectiveness and mother’s experiences of proactive person-centred telephone support after discharge. Furthermore, to describe the duration of breastfeeding and risks of ceasing breastfeeding up to 12 months. The first study, a register study with data from the Swedish Neonatal Quality register (SNQ), included breastfeeding data at discharge from 29 445 preterm infants born from 2004-2013. The results demonstrated that the prevalence of exclusive breastfeeding among preterm infants in Sweden decreased during the study period, especially among extremely preterm infants (<28 weeks). We also performed a multicentre randomised controlled trial (RCT) of 493 breastfeeding mothers of preterm infants discharged from six neonatal units in Sweden. The intervention consisted of a proactive breastfeeding telephone support system in which a breastfeeding support team called the mothers once everyday up to 14 days after discharge. The control group received reactive support; the mothers were invited to call the breastfeeding support team if they wanted to talk or ask any questions (i.e., usual care). The RCT demonstrated that the intervention did not affect exclusive breastfeeding at eight weeks after discharge (primary outcome) or up to 12 months. The proactive support did not affect maternal breastfeeding satisfaction, attachment, quality of life or method of feeding (secondary outcomes). However, parental stress was significantly reduced in mothers in the intervention group. Mothers in the intervention group were significantly more satisfied and involved in the support and felt empowered compared with mothers in the control group, who experienced reactive support as dual. Further findings showed that a lower maternal educational level, partial breastfeeding at discharge and longer stay in the neonatal unit increased the risk of ceasing breastfeeding during the first 12 months of postnatal age. In conclusion, the trend for exclusive breastfeeding at discharge in preterm infants is declining, which necessitates concern. The evaluated intervention of telephone support did not affect breastfeeding, in the short-or long-term. However, maternal stress was reduced and mothers were significantly more satisfied with the proactive support and felt empowered by the support.

Keywords: Breastfeeding, preterm infant, mother, support, prevalence

Jenny Ericson, Department of Women's and Children's Health, Akademiska sjukhuset, Uppsala University, SE-75185 Uppsala, Sweden.

ISSN 1651-6206 ISBN 978-91-513-0161-7 urn:nbn:se:uu:diva-333575 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-333575)

To mothers of preterm infants

List of Papers

This thesis is based on the following papers, which are referred to in the text by their Arabic numerals.

1. Ericson, J, Flacking, R, Hellström- Westas, L, Eriksson, M. (2016) Changes in the prevalence of breastfeeding in preterm infants discharged from neonatal units: a register study over 10 years. BMJ Open 2016;6: e012900. doi:10.1136/ bmjopen- 2016-012900 2. Ericson J, Eriksson M, Hellström-Westas L, Hagberg L, Hoddi- nott P, Flacking R. (2013) The effectiveness of proactive telephone support provided to breastfeeding mothers of preterm infants: study protocol for a randomized controlled trial. BMC Pe- diatrics, 2013:13;73 3. Ericson, J, Eriksson, M, Hellström-Westas, L, Hoddinott, P, Flacking R. (2017) Proactive telephone support provided to breastfeeding mothers of preterm infants after discharge: a randomised controlled trial. Submitted 4. Ericson, J, Eriksson, M, Hoddinott, P Hellström-Westas, L, Flacking, R. (2017) Breastfeeding duration in preterm infants and the long-term effects of telephone support: a randomized controlled trial. Submitted 5. Ericson, J, Flacking, R, Udo, C. (2017) Mother’s experiences of a telephone-based breastfeeding support intervention after discharge from neonatal intensive care units – a mixed-method study. Submitted

Reprints were made with permission from the respective publishers.

Contents

Introduction ...... 11 Benefits of breast milk ...... 11 Breastfeeding prevalence ...... 12 Preterm infant breastfeeding behaviours ...... 12 Mothers of preterm infants ...... 13 Breastfeeding experiences ...... 14 Transition to home ...... 14 Factors associated with early weaning ...... 15 Breastfeeding support ...... 16 Telephone support ...... 17 Theoretical framework ...... 17 Person-centred care ...... 17 Definition of breastfeeding ...... 18 Rationale ...... 18 Aim ...... 19 Specific aims: ...... 19 Methods ...... 20 Setting ...... 20 Design ...... 21 Study I (paper 1) ...... 21 Study II (paper 2-5) ...... 21 Data collection and participants ...... 22 Study I (paper 1) ...... 22 Study II (paper 2-5) ...... 23 Analyses ...... 27 Study I (paper 1) ...... 27 Study II (paper 2-5) ...... 28 Ethical considerations ...... 30 Study I (paper 1) ...... 30 Study II (paper 2-5) ...... 30 Results ...... 31 Study I (paper 1) ...... 31 Participating mothers and infants ...... 31 Breastfeeding prevalence ...... 33

Factors negatively affecting breastfeeding ...... 33 Study II (paper 3-5) ...... 38 Participating mothers and infants ...... 38 Effects of proactive breastfeeding support ...... 41 Breastfeeding and factors associated with the risk for ceasing breastfeeding ...... 43 Method of feeding...... 45 Mothers experiences of proactive and reactive support ...... 47 Discussion ...... 49 Summary of results ...... 49 Study I (paper 1) ...... 49 Study II (paper 2-5) ...... 50 Strengths and limitations of the studies ...... 52 Conclusion ...... 55 Future research and clinical implications ...... 56 Sammanfattning (in Swedish) ...... 57 Acknowledgments...... 60 References ...... 62

Abbreviations

BPD Bronchopulmonary Dysplasia GA Gestational Age MBFES Maternal Breastfeeding Evaluation Scale MPAS Maternal Postnatal Attachment Scale NEC Necrotizing Enterocolitis NICU Neonatal Intensive Care Unit PNA Postnatal Age RCT Randomised Controlled Trial ROP Retinopathy of Prematurity SES Socioeconomic Status SF-36 Short Form Health Survey, 36 items SGA Small for Gestational Age PSI Parental Stress Index SNQ Swedish Neonatal Quality register SPSQ Swedish Parental Stress Questionnaire WHO World Health Organization

Introduction

The best nutrition for the infant is breast milk, and the World Health Organi- zation (WHO) recommends initiation of breastfeeding within one hour after birth and exclusive breastfeeding for the first 6 months of life (1). Breast milk is even more beneficial in preterm infants, i.e., gestational age <37 weeks (GA) (2, 3). Despite an increasing awareness that breast milk is beneficial, many preterm infants may not receive breast milk during the first months of life (4, 5). For this reason, it is important to investigate the prevalence of breastfeeding and factors that affect breastfeeding in preterm infants and to create interventions to support breastfeeding in mothers of preterm infants.

Benefits of breast milk Breast milk is a complex biological compound that satisfies the infant’s nutritional requirements, modifies the infant’s immune system and protects against pathogens. Furthermore, breast milk promotes the infant’s neurological and metabolic development (2, 6-8). In the very preterm infant (GA <32 weeks), breast milk also has a protective effect against necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD) and late onset sepsis (3, 6). Breastfeeding is also associated with better neurological and cognitive development persisting to adolescence, including a higher IQ (9, 10). Hypotheti- cally, two major mechanisms are involved in the positive cognitive development related to breastfeeding: the optimal nutritional content of breast milk and the positive effects on the mother-infant relationship and interaction thereby indirectly supporting cognitive development (11). The protective properties in breast milk are the result of synergistic actions of many bioactive compounds such as, immune cells, fatty acids, human oligosaccharides, lyso- zyme, lactoferrin and commensal bacteria (7, 8, 12). There is a dose-response effect in that greater benefits are achieved with exclusive and longer durations of breastfeeding (10, 13, 14). It has been estimated that small changes in the prevalence of breastfeeding may also result in significant health differences for infants and mothers through changes in health, health care costs and economic productivity (15).

11 Breastfeeding prevalence The prevalence of breastfeeding varies between countries. In the Nordic countries, almost all mothers initiate breastfeeding while other countries, e.g., France and Ireland report initiation rates of less than 70% (16). However, during the period from 2004 to 2015, the prevalence of exclusive breastfeeding in all infants in Sweden decreased, at one week from 89 to 78%, at 2 months from 77 to 64%, and at 6 months from 19% to 15% (17). In contrast, the UK and the US report increasing breastfeeding prevalence (18, 19). Breastfeeding rates in preterm infants are much lower than in term infants (20). Furthermore, the proportion of very preterm infants who are exclusively breastfed is lower than in moderately preterm infants (GA 32-36 weeks) (21, 22), but there are wide variations in the preterm population (21, 23-25). In the late 20th century and early 21st century, France reported that less than 20% of very preterm infants were breastfed (any breastfeeding) at discharge (26), while in Sweden, more than 90% of preterm infants were breastfeeding at discharge (27, 28). However, there is a lack of studies investigating the duration of breastfeeding in preterm infants. In a Danish study from 2014 (4), the exclusive breastfeeding rates at 1, 4 and 6 months postnatal age (PNA) were 66%, 38% and 13%, respectively, in preterm infants. Furthermore, at 12 months of infant age 12% of the infants were partially breastfeeding (4). In a Swedish study on breastfeeding exclusivity in preterm infants at 2, 4, and 6 months of infant age, 51%, 37%, and 9% of the mothers breastfed, respectively (27). In another Swedish study, 12% of the preterm infants were partially breastfeeding at 12 months of age (29). However, there are no recent studies available on national trends in breastfeeding prevalence among preterm infants in Sweden.

Preterm infant breastfeeding behaviours Approximately 5% of infants are born preterm in Sweden (30), and the worldwide the incidence of preterm birth ranges from 5% to 18% (31). Of the preterm infants in Sweden, 5% are born extremely preterm (GA<28 weeks), 11% very preterm (GA 28-31 weeks), and 84% moderately preterm (GA 32-36 weeks) (31). Preterm infants show higher mortality and morbidity than term infants (32). Preterm infants are, depending on gestational age, immature in their sucking behaviour; have a weak suck and have difficulty coordinating breathing and swallowing, which delays the attainment of exclusive breastfeeding. However, preterm infants show early breastfeeding competence and can root, grasp the areola efficiently and perform short sucking bursts as early as 29 weeks, and can achieve nutritional breastfeeding beginning at 31 weeks (33). From the time of birth until infants can supply themselves nutritionally, mothers who want to breastfeed must express breast milk through pumping several times per day. Initially, the infants are usually fed their mothers’ breast

12 milk, donor or formula through a gavage tube. When the infants become more mature, feeding directly at the breast increases, feeding through the gavage tube decreases and eventually the infants support themselves directly at the breast and/or by bottle. This transition period from tube feeding to breastfeeding/bottle feeding varies in length. There is a lack of knowledge for supporting mothers/infants in the transition from tube feeding to breastfeeding, and care is regulated by non-evidence-based guidelines and routines (34). During the transition period from tube feeding to breastfeeding, the mothers cannot take part in their infants’ nutrition in the same way as parents of healthy infants born at term, and they are often dependent on infant maturity and neonatal staffs’ advice and support.

Mothers of preterm infants Preterm infants usually require care at a neonatal unit and/or a neonatal intensive care unit (NICU) for a few days up to several months. This constitutes a situation in which the maternal role and breastfeeding begin and develop in an unfamiliar medical setting. It may take time for mothers to understand their maternal role, and they may experience stress, helplessness, and fear about the infant’s health, as well as shame or guilt because of the preterm delivery (35). The neonatal unit stay may also place strain on the family, and the changes in family dynamics related to the new-born infant are also more pronounced for these parents (35). Mothers of preterm infants may experience initial difficulties in the transition of becoming a mother (36, 37) and are at risk for experiencing less positive interactions and attachment during the first 6 months after birth compared with mothers of term infants (38). Feelings that may contribute to these difficulties are worries for the baby, exclusion, a dis- connection from the child, maternal inadequacy, and the unfamiliar environment of the neonatal unit. These feelings may be more prominent if the mother feels that the staff are in charge of her infant’s care, that she is not able to take care of and protect her infant, or if there is a lack of emotional and physical contact with the infant (39, 40). The physical environment of the neonatal unit also plays a role in the process of becoming a mother. Open-bay units in which the nurses are constantly present may render a situation in which mothers “mimic” staff and mothers are struggling to be perceived as “a good mother” (36, 41). However, over the last decade many Swedish neonatal units have been redesigned to single family rooms to provide increased privacy, increased parental involvement in patient care, improved sleep, decreased length of hospital stay, and reduced re- hospitalisation (42).

13 Breastfeeding experiences For many mothers an important aspect of becoming a mother is breastfeeding (43, 44). Awareness of the benefits of breastfeeding motivates, encourages and commits mothers of preterm infants to express breast milk and to continue breastfeeding. Society and societal norms also play a role in the breastfeeding experience, where pro-breastfeeding societies are supportive for breastfeeding but may also increase the mother’s perceived sense of duty to breastfeed (41). In other societies, the norm of breastfeeding is less evident. In such contexts, the beneficial effects of breast milk may be equally argued whilst breastfeeding, especially in public, is less accepted, which may render a situation of “shame if you do [breastfeed] and shame if you don’t [breastfeed]” (45). Establishment of lactation and expression of breast milk after a preterm delivery may be unfamiliar and demanding tasks to cope with for many mothers and are described as frustrating, inconvenient, physically painful and ex- hausting (46). However, breastfeeding may also be experienced as a means, to compensate for the preterm birth and feelings of guilt (47). Breastfeeding, with its physical closeness, is described as a step towards normality, a healing state, an enjoyable bonding experience and part of being a mother (37, 44, 46, 47). Nevertheless, some mothers struggle with breastfeeding problems during neonatal care, including difficulties related to infant latching, positioning, breast refusal, low milk supply, breast complications, slow progression in the transition from tube feeding to breastfeeding, and difficulties coordinating everyday life (46). For many mothers, discharge from the hospital is a new beginning and an opportunity for breastfeeding. These mothers are highly mo- tivated and every step towards advancement in breastfeeding creates positive feedback (44). However, some mothers hope that breastfeeding will be easier at home, but where they experience unfulfilled information needs and varying support (44). According to the mothers, concerns about milk intake and post discharge growth, breastfeeding techniques and infant sleepiness are the most common breastfeeding problems after discharge, which may persist up to 3 months of corrected age (46). The mothers report that the most important factors for successful breastfeeding are support from the environment, their emotional state and the amount of stress experienced (44). As breastfeeding is an important part of being a mother, mothers feel proud when breastfeeding is successful and disappointed when breastfeeding is unsuccessful (44).

Transition to home After discharge, mothers may experience stress, especially in their perceived maternal role experience (48). The emotional impact of the neonatal unit experience may continue during the transition from the neonatal unit to home (49). For many mothers of preterm infants, this transition has been described

14 as difficult, in general and in terms of breastfeeding, due to lack of support and unsolved problems (e.g., infant sleepiness, difficult in latching, low milk supply) (41, 44, 50). Particularly vulnerable are infants of mothers with lower socioeconomic status (SES) (29, 51). Mothers’ experiences of parenting after discharge from the neonatal unit may alternate between worrying/insecurity and confidence/security (41, 49). Factors such as infant health, the family situation or health professional support contribute to either worrying/insecurity or confidence/security (49). Improved support to families after discharge from the neonatal unit is suggested as crucial for attaining the maternal role and helping families with the transition to the home environment (52-55). By decreasing the stress experienced by mothers through support, the transition to home may be facilitated (48) and thus increase breastfeeding, breastfeeding satisfaction, quality of life and attachment to the infant.

Factors associated with early weaning Mothers’ intention to breastfeed, feeling of self-efficacy and absence of postpartum depression are strong predictors of exclusive breastfeeding (56). Other factors, such as support from next of kin and health care professionals (57), socio-cultural (5, 43, 58), health care attitudes (43, 59, 60), and infant factors (28) (i.e., GA, infant temperament and infant suckling) can also affect the breastfeeding duration. Moreover, several studies have shown a significant relationship between higher SES and longer breastfeeding duration (20, 61- 63). In a previous Swedish study, 87% of mothers with a higher education were breastfeeding their preterm infant at two months PNA compared to 80% of mothers with an upper secondary school education and 58% of mothers with compulsory school or less (62). For many mothers, weaning occurs during the first weeks at home (64). Undesired weaning, due to difficulties with latching, pain and milk supply are, according to mothers, the most common reasons to stop breastfeeding. This may be an effect of breastfeeding physiology (65). The stress that mothers of preterm infants can experience may increase the exposure of these mothers to breastfeeding difficulties. Insufficient milk supply is a common concern both in the neonatal unit, at discharge and after discharge, and according to mothers, an insufficient milk supply is related to their anxiety, dependence on the breast pump for expressing milk, and mood swings (46). Insufficient milk supply is associated with feelings of frustration, failure, and disappointment and can reduce maternal confidence. Advice such as more frequent pumping, special food and medications are experienced as insufficient by mothers (46). Mothers make the decision to cease breastfeeding when the breastfeeding problems become overwhelming. Some mothers have negative feelings, such as guilt, failure, disappointment and doubts, about discontinuing breastfeeding (46, 47). Other mothers have positive feelings, such as satisfaction, freedom,

15 an improved relationship with the infant, and satisfaction are related to a re- sumed routine (46).

Breastfeeding support In general, social support provide positive health states, for example personal competence, psychological well-being, decreased depression and anxiety and effective coping behaviours. Social support may be divided in four different types of support: instrumental provision of assistance, material, money or services, emotional offering empathy, encouragement, trust or caring, informa- tional providing advice, suggestions or guidance and affirmational give someone a sense of social belonging (66). In previous studies, social support, including these components, have shown to be important for breastfeeding (67- 69). Moreover, there is a substantial amount of research showing that when support is offered to mothers, the duration and exclusivity of breastfeeding increases (70). It is suggested that effective breastfeeding support should be performed by trained staff during postnatal care through scheduled visits so that mothers can predict when support will be available, and tailored to the setting and the needs of the population group (70). Mothers view the neonatal unit as an important place for breastfeeding support. Some mothers are satisfied with the provided support, while others are not. The reasons why mothers are dissatisfied include unmotivated nurses, lack of support and being left alone in their breastfeeding efforts (44). Schmied et al (71) suggest that the reasons for inadequate health care support are time pressure, insufficient staffing and unhelpful practices. After discharge, mothers with breastfeeding problems indicated that they did not receive the help they needed (47). A qualitative meta-synthesis of women’s experiences shows the importance of providing person-centred care to support breastfeeding (71). Per- son-centred communications skills and relationships are important for supporting the mother in her breastfeeding efforts. An authentic presence and a facilitative approach, which involve supportive care and a trusting relationship, are perceived as helpful among mothers who want to breastfeed. The organisation systems that offer models of continuity of care are more likely to facilitate an authentic presence since they build relationships. It is important for supporters to achieve a balance in their approach that is positive but realistic, encouraging, proactive, and focuses on benefits without creating pressure on mothers to breastfeed. Mothers feel that they have support when they are being listened to with empathy and receiving detailed and realistic information centred on their needs and encouragement and affirmation (71).

16 Telephone support Telephone support has been previously used for support in health care and a systematic review of peer support calls showed that it might be effective for certain health-related concerns (72). Furthermore, a systematic review con- cluded that telephone support may increase women’s overall satisfaction with their care; women who received support during pregnancy and shortly after birth had lower average depression scores in the postnatal period and a longer duration of breastfeeding (73). There are few published proactive telephone interventions supporting breastfeeding following hospital discharge. One pilot study evaluating proactive support in disadvantaged mothers with full-term infant after discharge from the maternity ward showed promising results for increasing breastfeeding (74).

Theoretical framework Person-centred care To reflect the importance of person-centred care when supporting mothers of preterm infants in breastfeeding, the theoretical framework of person-centred care influenced this thesis. Research has shown that mothers prefer breastfeeding support to be person-centred, which involves supportive care, continuity of care, and the development of trusting relationships (71). This finding is consistent with McCormack and colleagues’ (75, 76) framework of person- centred care. The framework comprises four constructs: prerequisites that focus on the characteristics of the support person, the care environment that focuses on the context, the person-centred process that focuses on delivering support and the expected outcomes. The prerequisites (i.e., characteristics) of the one who is delivering the support include that (s)he has self-awareness and that (s)he has professional competence and have developed interpersonal skills. Furthermore, (s)he must be committed to the job and have clarity of his/her beliefs and values. The characteristics of the care environment include, for example, the physical environment, the workplace culture and the mixed and innovative skills of the staff. Additionally, shared decision-making should be well established in the environment. The person-centred process includes components such as building mutual trust and understanding, treating the person as an individual, respecting the rights of the person, sharing decision-making and providing holistic care. Fur- thermore, the care provider should engage with and have a sympathetic presence with the person.

17 It is suggested that expected outcomes of effective person-centred care are increased satisfaction with care, involvement in care, and a feeling of well- being that creates therapeutic relationships (76).

Definition of breastfeeding In this thesis, the term breastfeeding was used both for breastfeeding at the breast and for breast milk feeding by bottle, tube, or cup (1), unless otherwise stated.

 Exclusive breastfeeding: feeding with only breast milk regardless of feeding method, but could include medications, fortification and vit- amins.  Partial breastfeeding: feeding with breast milk in combination with formula and/or solid food feeding.  No breastfeeding: solely formula and/or solid food feeding with no breast milk intake.

Rationale Breastfeeding has a great impact on preterm infants’ health and development. However, breastfeeding prevalence in the general population is declining in Sweden, and research has shown that breastfeeding prevalence is lower in preterm infants than in infants born at term. However, there is a lack of knowledge on how the breastfeeding prevalence in preterm infants has developed during the last decade. Furthermore, more research is needed to explore potential factors that could influence breastfeeding at discharge and long-term. The transition to home and breastfeeding may be stressful and a complex process for mothers of preterm infants, involving factors such as psychology, physiology and context. The research is limited on evaluating interventions that aim to support breastfeeding after discharge from the neonatal unit. There- fore, it was hypothesised that through intervention by proactive breastfeeding telephone support, exclusive breastfeeding would increase, along with maternal satisfaction with breastfeeding, attachment and quality of life and that parental stress would decrease compared with only reactive support.

18 Aim

The overall aim of this thesis was to describe the prevalence of breastfeeding in preterm infants and to evaluate the effectiveness and mother´s experiences of a proactive person-centred telephone support after discharge. Furthermore, to describe the duration of breastfeeding and risks for ceasing breastfeeding up to 12 months postnatal age.

Specific aims: Study I (paper 1) To investigate trends in exclusive breastfeeding prevalence at discharge from Swedish neonatal units and associated factors in preterm infants from 2004 to 2013.

Study II (paper 2) To describe the study design of a multicentre randomised controlled trial on proactive breastfeeding telephone support.

Study II (paper 3) To evaluate the effectiveness of a person-centred proactive telephone support on breastfeeding and on maternal satisfaction with breastfeeding, attachment to the infant, maternal stress and quality of life at eight weeks follow-up after discharge from neonatal intensive care units.

Study II (paper 4) To evaluate the effectiveness of a person-centred proactive telephone support on breastfeeding and mothers’ choice of feeding method and to describe the risks for ceasing breastfeeding up to 12 months postnatal age.

Study II (paper 5) To describe mothers of preterm infants’ experiences of proactive and reactive breastfeeding telephone support after discharge from neonatal intensive care units.

19 Methods

Setting In Sweden, neonatal care is offered at 29 local and county hospitals (level I- III care) and eight university hospitals (level I-IV care) (77). Preterm infants with GA <35 weeks are most often cared for in neonatal units, and infants with GA 35-36 weeks are usually cared for at maternity units, unless they have medical problems, in which case they are admitted to neonatal units. In Swe- dish neonatal units, parents may stay with their preterm infants at all hours (78). Many units have family rooms where the family can stay with their infants for the whole hospitalisation. The neonatal units provide various degrees of Kangaroo Mother Care (KMC) (79) and the Newborn Individualised De- velopmental Care and Assessment Program (NIDCAP). Almost all preterm infants in neonatal units receive the mother or donor’s milk during the first weeks of life. Some infants receive their mother’s milk or donor’s milk throughout the stay in the neonatal unit, and others for just a few weeks. The neonatal units have either their own milk bank or access to a central breast milk bank for the mother’s own or donor breast milk (80). In Swedish neonatal units, almost all preterm infants are tube fed (or cup fed) until breastfeeding (i.e., feeding directly at the breast) and/or bottle-feeding is established. A daily volume of nutritional and fluid needs (i.e., breast milk, formula and/or fortification) is prescribed with a target volume of 170-200/ml/kg (81). This daily volume is dependent on the infant’s weight gain, age in days from delivery, and the infant’s medical condition. The daily prescribed volume is divided by the number of feedings appropriate for the infant’s age and well-being. The infants’ sleep-wake states and feeding cues are acknowledged, whereby infants can be fed (either directly at the breast and/or by tube) based on their signals rather than at scheduled times. The neonatal units use care routines, such as “estimated breastfeeding”, test weighing (82) or similar techniques, to estimate how much supplement is needed by the infant after breastfeeding. When the infant matures and can increasingly orally supply itself, the amount of supplementation is decreased until the infant is fully on demand breastfeeding and/or bottle-feeding and is gaining weight. The tube is, then removed. The participating NICUs in this thesis enabled parents to go home with their infant before hospital discharge and to tube feed the infant at home with different types of support from the NICU, i.e., domiciliary care. In two NICUs, the domiciliary care was organised so that a nurse visited the families at home;

20 in three NICUs, the families travelled to the NICUs for care and follow-up; and in the sixth NICU, they changed from the first to the latter during the study period. In Sweden, both the mother and the father are eligible to receive paid sick leave when the infant is cared for in the hospital.

Design Study designs, populations and methods for data collections are outlined in table I.

Study I (paper 1) Study I was a register study with data from the Swedish Neonatal Quality register (SNQ).

Study II (paper 2-5) Study II was a multicentre randomised controlled trial (RCT) following the CONSORT recommendations and is registered at www.clinicaltrials.gov (NCT01806480). We hypothesised that proactive telephone support offered to breastfeeding mothers of preterm infants after hospital discharge was more effective than reactive telephone support (i.e., mother initiated, and defined as usual care) for increasing the proportion of mothers who were exclusively breastfeeding at eight weeks after discharge. A detailed description of the study design is provided in paper 2. Paper 3 presents the primary outcome, while paper 4 focuses on secondary outcomes. In paper 5, a qualitative-driven concurrent embedded mixed-method approach was used, in which the data were triangulated with equal priority.

Protocol In papers 3-5, six level IIIa or IIIb NICUs participated in the RCT (Falun, Karlstad, Skövde, Sunderbyn, Trollhättan, Örebro). At each NICU, a breastfeeding support team (10 staff/unit) was educated for two days on breastfeeding, person-centred care and trial design. The breastfeeding support team re- cruited, randomised and delivered the telephone support to participating mothers. The study was performed from March 2013 to December 2015.

21 Table 1. Outline of the study designs.

Study Paper Design Subjects Data collection I 1 Register study 29 445 preterm infants The SNQ register II 2 Study protocol RCT II 3-4 Multicentre random- 493 mothers of preterm Telephone follow-up ised controlled trial infants and self-reported questionnaires II 5 Mixed Method Written comments from Self-reported questionnaires, mothers (n=274) and 26 open-ended questions and tel- telephone interviews with ephone interviews mothers

Data collection and participants Study I (paper 1) The SNQ is a national quality register that started in 2003. In 2004, 30 neonatal units reported data, and in 2013, all 37 neonatal units in Sweden registered data in the SNQ. The data for each infant were collected from standardised questionnaires prospectively filled out at admission and at discharge by a phy- sician. Thereafter, a secretary entered the questionnaire information into the SNQ-database and usually checked possible inaccuracies. The SNQ register includes data on maternal characteristics, pregnancy, delivery, hospital stay, neonatal illness, diagnoses classified by ICD-10 and discharge data. This study included all preterm infants (GA <37 weeks) who had data on breastfeeding at discharge in the SNQ register from 2004 to 2013. The following maternal variables were collected from the register: maternal illness, gestational diabetes and preeclampsia, which were pre-stated items with a yes/no alternative. In addition, all text related to mental illness (e.g., anxiety, depression, bipolar disorder) was retrieved from a free text space where a range of diseases, such as diabetes, hypertension and mental illnesses, were specified. The following infant data were collected: birth year, multiple birth, mode of delivery (caesarean section/vaginal), GA, birth weight, small for gestational age (SGA, defined as a birth weight less than -2 standard deviations from the mean according to the Swedish standard), sex and feeding status at discharge (i.e., exclusive, partial and no). The following neonatal morbidities were included: BPD, defined as the need for additional oxygen at 36 gestational weeks), retinopathy of prematurity (ROP), any degree, and necrotizing enterocolitis (NEC).

22 Study II (paper 2-5) Study protocol Paper 2 is a published study protocol that provides a detailed description of the design and methods in the RCT. The study design followed the CONSORT recommendations for reporting an RCT (83). The study protocol describes the background and rationale for the RCT. The following information was presented: calculated number of participants (sample size), eligibility and exclusion criteria and details of the intervention to be received by the participants. Demographic information about the participants to collected, and primary and secondary outcomes were also presented. The purpose of the protocol was to ensure the scientific quality of the study and that the findings would be reliable and valid.

Data collection at the unit Each unit kept a logbook, in which the breastfeeding support team recorded data on all infants admitted to the NICU, admission date, gestation week, eligibility for inclusion, date assessed for eligibility, reason for exclusion and whether mothers that declined participation had been asked to voluntarily answer some baseline characteristic questions. At times of inclusion and discharge, a breastfeeding support team member filled in established data proto- cols on demographics, infant health and breastfeeding. If any mothers dropped out of the trial between informed consent and hospital discharge, the reasons were recorded if the mother consented to provide such information. After hospital discharge, randomisation generated the group allocation, which was entered into the logbook. Only the breastfeeding support teams in each unit were aware of the allocated group for each mother.

Data collection after discharge Jenny Ericson, who was blinded to the group allocation for the primary outcome, performed the project coordination and data collection at follow-up (eight weeks after discharge, 6 and 12 months PNA) by telephone and questionnaires. At all follow-ups, a letter was attached to the questionnaire in both the intervention and control groups asking the mothers to participate in an interview regarding their experiences of the telephone support. Mothers whose infants had been discharged for more than eight weeks and less than 24 weeks were, during spring 2016, invited again by a call from a researcher to participate in a telephone interview. All mothers invited by telephone consented to be interviewed, and individual telephone interviews were conducted for 26 mothers: intervention group (n=8) and control group (n=18). The researchers (i.e., Jenny Ericson, supervisors and statistician) were at this time blinded to the treatment assignment.

23 Participants Eligible participants for randomisation were breastfeeding mothers with preterm infants (GA<37 weeks) who had been admitted >48 hours to one of the participating NICUs. Exclusion criteria were serious maternal medical or psy- chiatric problems at discharge, language problems that could not be resolved, infants that were transferred to another hospital/unit after discharge or infants that were terminally ill.

Intervention

Intervention group The intervention group received proactive telephone support i.e., daily phone calls to the mother from a member of the breastfeeding support team at the NICU from which the infant was discharged from day 1 until day 14 after discharge. In addition, the mother had the option to call someone in the breastfeeding support team during the same period (i.e., reactive telephone support). The intention was that the telephone support should have a person-centred approach, according to Schmied et.al. (71) and McCormack et.al. (84). Fur- thermore, the support aimed to provide continuity of care. Thus, the mothers were enabled to talk about whatever they felt was important.

Control group The control group was offered the opportunity for person-centred reactive telephone support initiated by the mother, who could phone the breastfeeding support team from day 1 until day 14 after discharge between 08.00 and 16.00 every day (including weekends). Reactive support was defined as ‘usual care’. The intention was that the mothers in the control group should receive the same level of person-centred care as mothers in the intervention group, if they chose to contact the breastfeeding support team.

Primary outcome Exclusive breastfeeding The primary outcome was exclusive breastfeeding eight weeks after hospital discharge. Data were collected by a telephone follow-up by Jenny Ericson. Furthermore, the same questions were asked in a questionnaire sent to the mothers concurrently (table 2).

Secondary outcomes Data were collected through telephone follow-ups and questionnaires sent to the mothers eight weeks after hospital discharge, 6 and 12 months PNA (table 2).

24 Breastfeeding Breastfeeding and breastfeeding duration were measured as exclusive, partial or no breast milk at all follow-up times.

Method of feeding The method used to give the infant breast milk; it could be directly at the breast, by bottle, cup, or tube or in different combinations.

Factors associated with risk for ceasing breastfeeding The risk factors analysed for ceasing breastfeeding were the mother’s educational level, parity, mother’s birth country if it was other than Sweden, mode of delivery, multiple births, gestational age at birth and SGA. Furthermore, length of stay, group allocation and domiciliary nursing care (i.e., parents care for the infant at home before hospital discharge receiving support from the NICU) were also assessed.

Mother’s experiences The mother’s experiences of proactive and reactive breastfeeding telephone support were collected through written comments in questionnaires sent to the mothers and by 26 telephone interviews performed 2-6 months after discharge.

Mothers’ satisfaction with breastfeeding The mother’s satisfaction with breastfeeding was measured with the Maternal Breastfeeding Evaluation Scale (MBFES) (85). The scale includes 30-items with three dimensions: maternal enjoyment and role attainment, infant satisfaction and growth, and lifestyle and maternal body image. The items were scored on a five-point scale from strongly disagree to strongly agree. A summary score was calculated with a minimum of 30 and maximum of 150 scores. Higher scores indicate a more positive breastfeeding experience. The psychometric properties of the MBFES are robust; Cronbach´s alpha (internal consistency) has been described to range from 0.77-0.94 in different countries (85, 86). As there was no Swedish version of the scale, a translation was performed according to guidelines and standards for the translation and cultural adaptation of patient-reported outcome measures suggested by Wild et al (87). The scale was translated from English to Swedish by a professional Swedish- speaking translator, reconciled, and then translated back to English by a professional English-speaking translator and then again back to Swedish. Jenny Ericson and Renée Flacking performed a revision and harmonisation of the translation before final proofreading. The Cronbach’s alpha for the MBFES was 0.93 at all follow-ups in the present study.

25 Maternal postnatal attachment The mother’s maternal postnatal attachment was measured with the Maternal Postnatal Attachment Scale (MPAS) (88), which includes 19-items with three dimensions: quality of bonding, absence of hostility, and pleasure in interactions. The items were scored on a two, four or five-point scale that provided a total global attachment score of 19-95. Higher scores indicate higher mother- to-infant attachment. The psychometric properties of the MPAS have been robustly reported from use in different settings (countries and populations) with high internal consistency (Cronbach’s alpha between 0.75-0.78) and strong test-retest reliability (r=0.86) (88, 89). As there was no Swedish version of the scale, the scale was translated according to the same procedure described for MBFES. The Cronbach’s alpha for the MPAS in the present study was 0.78, 0.76 and 0.79 at the 8-week, 6 and 12-month follow-ups, respectively.

Parental stress Parental stress was measured with the Swedish Parenting Stress Questionnaire (SPSQ)(90), which is a modified Swedish version of the Parenting Stress In- dex (PSI) (91). The scale includes 34-items with five dimensions: role restriction, incompetence, social isolation, health problems and spouse relationship problems. The items were scored on a five-point scale from strongly disagree to strongly agree. Scale scores were calculated as the mean for each dimension, and the total score was calculated as the mean of all responses. Higher scores indicate higher perceived parenting stress. The SPSQ has been found to have good validity and reliability in a Swedish context (90). The Cronbach’s alpha for the SPSQ in this present study was 0.90, 0.89 and 0.90 at the 8-week, 6 and 12-month follow-ups, respectively.

Quality of life The mother’s quality of life was measured with the Short Form Health Survey (SF-36) (92). The scale includes 36-items with eight health dimensions: physical functioning, social functioning, bodily pain, vitality, general health, mental health, role-physical, and role-emotional. SF-36 provides an assessment of the mother’s physical function, subjective well-being and general health during the prior four weeks. All domains are scored on a scale from zero to 100, where higher scores indicate better health. SF-36 has been found to have good psychometric properties in different countries, including Sweden (92). The Cronbach’s alpha for the SF-36 in this present study was 0.91, 0.92, 0.92 and 0.94 at baseline and 8-week, 6 and-12 month follow-ups, respectively.

26 Table 2. Outline of time points for follow-up and outcomes in study II. Outcome measure Baseline 8 weeks’ after 6 months 12 months After end discharge PNA PNA of recruitment Breastfeeding (exclusive or partial/no) x x x x Breastfeeding duration x x x x Method of feeding x x x x Factors associated with cessation of x x x x breastfeeding

Mothers experiences (questionnaires x x x x x and telephone interviews)

Attachment (MPAS) x x x Mothers’ satisfaction with breastfeed- x x x ing (MBFES) Parental stress (SPSQ) x x x Quality of life (SF-36) x x x x

Randomisation process Mothers who met the inclusion criteria and who provided consent were randomised to either the intervention or the control group. Each mother was as- signed an identification code when they consented to participate. The randomisation was conducted by the breastfeeding support team within 24 h from discharge by an automated and secure web-based system administered inde- pendently of the research team. A stratified block randomisation was used, with blocks of 25 high SES and 25 low SES mothers at each participating NICU. The mothers were informed of their randomisation group immediately following randomisation by a telephone call or text message.

Analyses In both studies (I + II), descriptive data are presented as numbers and propor- tions. Data from the logistic and Cox regression models are presented with odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (95% CIs). In all quantitative analyses, the statistical significance level was set at p <0.05 and calculations were performed with SPSS version 21.0 (Armonk, NY: IBM Corp.).

Study I (paper 1) Analyses of changes in prevalence and factors negatively affecting breastfeeding were performed for the whole population and for each of the three GA groups: extremely, very and moderately preterm infants. Unadjusted logistic

27 regression analyses were conducted to assess the trend in breastfeeding from 2004 to 2013. Furthermore, unadjusted analyses were used to investigate whether there was a statistically significant increase or decrease in each inde- pendent variable for exclusive versus no/partial breastfeeding at discharge and to investigate the variables effect on breastfeeding. In the next step, factors that were significantly negatively associated with exclusive breastfeeding and that showed a significant increased trend over time were included in the adjusted logistic regression analyses. The OR represents the average difference over time for not breastfeeding exclusively. Due to few cases, the factors gestational diabetes (n=13, 0.7%) in the extremely preterm group, and BPD (n=23, 0.1%) and NEC (n=26, 0.1%) in the moderately preterm group were excluded from the regression analyses.

Study II (paper 2-5)

Power calculation and sample size Earlier data indicated that the exclusive breastfeeding rate at two months of corrected age in preterm infants was 53%. With an estimated 8.5% increase in exclusive breastfeeding and an estimated dropout rate of 5%, the total sample size needed to be 1116 mothers, with 558 in the intervention group and 558 in the control group. Due to time constraints, we were only able to include 493 mothers of preterm infants in the study until inclusion was terminated.

Quantitative analyses Analyses were conducted according to intention-to-treat principles, in which all randomised mothers were included in the groups to which they were allocated, regardless of the number of telephone calls they received and/or made, if data were available for follow-up. Group similarity and comparability between the intervention and control groups were assessed based on maternal and infant characteristics. Normally distributed variables were analysed using Student’s t-test with the mean and standard deviation. Non-normally distributed variables were analysed using the Mann-Whitney U-test with the median and interquartile range. To show differences in the proportion of dichotomous variables, the chi-square test was used. Adjusted logistic regression analyses were used to study the effects of the intervention on breastfeeding, in which the OR represents the odds for not breastfeeding exclusively at discharge at eight weeks after discharge, 6 and 12 months PNA, in the control group compared with the intervention group. The regression model was adjusted for maternal educational level and site as stratified in the randomisation. Another regression model was also performed in which we adjusted for breastfeeding at discharge. Subgroup analyses were conducted of the mother’s educational level (secondary school or less versus higher education), parity (primipara versus multipara), and gestational age (<

28 32 weeks versus 32-36 weeks) using unadjusted logistic regression analysis of the primary outcome. Exclusive breastfeeding prevalence was compared to partial/no breastfeeding (i.e., partial and no breastfeeding were merged into one group) in all logistic regression analyses. Unadjusted and adjusted HR were used to study the risk for ceasing breastfeeding (event) during the first 12 months PNA using Cox proportional hazard regression. Time was determined as the number of days of breastfeeding. In the Cox regression analyses, the HRs represent the probability of ceasing breastfeeding during the first 12 months PNA. A backward stepwise approach was used to identify confounders, with variables retained at p<0.05 (Wald test). To analyse the effects of the intervention on breastfeeding satisfaction, attachment, parental stress and quality of life, Student’s t-tests were performed. For the scales, the total score and dimension scores were compared between the intervention and control group for each scale. Imputation was conducted to replace missing items, in which the mean or median score on a dimension was used. Very few items were missing at 0.3% (n=146/44110). Effect size was calculated with Cohen’s d (d=0.2 small, d=0.5 medium, d=0.8 large) for secondary outcomes using the means and standard deviations of the intervention and control groups. Cronbach’s alpha was calculated for all scales to evaluate the reliability (i.e. internal consistency) for the scales. A Cronbach’s alpha greater than 0.7 represents high internal consistency.

Mixed method analyses A mixed method analysis is well suited to gain a deeper understanding and address a question at different levels (93, 94). To analyse the quantitative data for the difference between the intervention and control groups in terms of involvement and satisfaction with the breastfeeding support, Student’s t-tests was performed. To analyse the qualitative data, a thematic network analysis, inspired by Attride-Stirling (95), was used. The transcribed text from the telephone interviews and the written text from the open-ended questions in the questionnaires were read together several times. As a first step to reduce the text, segments of the text were identified guided by the aim of the study and coded. The coded text was organised into preliminary basic themes. The basic themes were then discussed between the authors and redefined during discus- sions before being merged and arranged into five preliminary organising themes. These organising themes were discussed among all authors and rear- ranged, keeping close to the original text and original expressions, before two global themes were deduced. All steps in the analytic process and all analytical decisions were continuously reflected upon and discussed among all authors until a consensus was reached.

29 Ethical considerations Study I (paper 1) All Swedish neonatal units participate in the data collection for the SNQ register, which is a quality register, aiming to improve neonatal care. The register aims to secure mothers’ and infants’ dignity and privacy and risk for participating mothers and infants were small. Parents are informed during the hospital stay that perinatal data are collected in the register and that they can decline collection of data or withdraw collected data at any time. Data were retrieved from the register in a password-protected data file. Each infant had an identification code that could not be traced to a specific person. All reporting occurred at the group level, where individual infants and mothers could not be identified. The Regional Ethical Review Board in Uppsala approved the study (Dnr: 2014/161).

Study II (paper 2-5) The included mothers and infants are considered a particularly vulnerable group from a research ethical perspective. It was important to secure the mothers’ and their infant’s health, dignity and privacy. The study had no obvious risks; the trial was conducted and monitored to minimise harm. All eligible mothers who agreed to participate in the study signed a written consent after receiving oral and written information. The mothers were informed that participation in the study was voluntary and that they could withdraw at any time. The mothers and infants’ confidentiality were ensured at all stages of the research process; no information in published articles or other reports of the study can be traced back to the mother or infant. The logbook, questionnaires, and recorded telephone calls were stored in a locked area that was not acces- sible to unauthorised individuals. The benefits of the project were high for this group, both for the mothers and infants involved and for future patients. How- ever, an ethical dilemma was that mothers might experience that they ended up in the wrong group, and as a result, in addition to the different approaches used by the NICUs to provide mothers an opportunity for support after discharge, reactive support was offered to both groups. Furthermore, there was apprehension that mothers would feel pressured and controlled by the staff if the intervention period was too intensive and/or long. Thus, an intervention period of two weeks was chosen. The study was also designed to be manage- able for the NICUs and easy to implement in a NICU setting. The Regional Ethical Review Board, Uppsala, approved study II (Dnr: 2012/292 and 2012/292/2).

30 Results

Study I (paper 1)

Participating mothers and infants Study I included 29 445 preterm infants, and a flowchart showing the included and excluded infants is shown in figure 1. The characteristics of participating mothers and infants are shown in table 3.

Figure 1. Flowchart of included and excluded infants in study I. Data from the Swe- dish Neonatal Quality register (2004-2013).

Table 3. Characteristics of 29 445 preterm infants discharged from Swedish neonatal units in 2004-2013. Data from the Swedish Neonatal Quality register (SNQ). Extremely preterm Very preterm Moderately preterm (GA 22-27 weeks) (GA 28-31 weeks) (GA 32-36 weeks) Total n=1 936 n=4 595 n=22 914 N=29 445 Demographic variables No % No % No % No % Maternal mental illness 59 3% 153 3% 828 4% 1040 4% Gestational diabetes 13 0.7% 65 1% 483 2% 561 2% Preeclampsia 240 12% 895 20% 3040 13% 4175 14% Administration of antenatal corticosteroids 1667 86% 3464 75% 4297 19% 9428 32% Multiple birth 499 26% 1310 29% 5361 23% 7170 24% Caesarean section 1186 61% 3143 68% 10079 44% 14408 49%

Gestational age at birth (weeks; median) 26 (1.3) 30 (1.1) 34 (1.3) 34 (2.8) Birth weight (grams; mean ± SD) 850 (214) 1460 (338) 2416 (533) 2164 (694) Small for gestational age 162 8% 502 11% 1621 7% 2285 8% Male sex 1017 53% 2490 54% 13463 54% 15970 54% Bronchopulmonary dysplasia 1056 55% 319 7% 23 0.1% 1386 5% Retinopathy of prematurity (any) 917 47% 219 5% 0 0% 1136 4% Necrotizing enterocolitis 132 7% 60 1% 26 0.1% 218 0.7%

Length of stay (days; mean ± SD) 96 (34) 47 (21) 16 (11) 26 (27) SD = standard deviation

Breastfeeding prevalence The prevalence of exclusive breastfeeding at discharge from hospital decreased significantly in Swedish preterm infants from 2004 to 2013 (paper 1). During the study period (2004-2013), the proportion of exclusive breastfeeding in extremely preterm infants decreased from 55% to 16%, in very preterm infants from 41% to 34% and in moderately preterm infants from 64% to 49% (p<0.05 for all three gestational age groups) (figure 2). In the whole study population, 15% of the infants were not breastfeeding at discharge from the neonatal unit in 2013, which is an increase from 12% in 2004. The decline in exclusive breastfeeding persisted after adjusting for factors that negatively affected breastfeeding prevalence and increased in the proportion during the study period from 2004-2013, i.e., maternal mental illness from 2% to 6%, administration of antenatal corticosteroids from 31% to 34% and infants born SGA from 4% to 9%.

Figure 2. Exclusive breastfeeding at discharge from neonatal units in three gestational age groups: extremely (n=550), very (n=1 848) and moderately (n=12 958) preterm infants. Data from the Swedish Neonatal Quality register (2004-2013).

Factors negatively affecting breastfeeding Factors in paper 1 that affected exclusive breastfeeding negatively included the infant birth year, multiple birth and SGA in all three GA groups. For extremely preterm infants, NEC also affected breastfeeding negatively (table 4). For very preterm infants, maternal mental illness, caesarean section, BPD and NEC were found to affect breastfeeding negatively (table 5). For moderately infants, maternal mental illness, gestational diabetes, preeclampsia, antenatal

33 corticosteroids and caesarean section were found to affect breastfeeding negatively (table 6). Factors that affected exclusive breastfeeding negatively and that had increased during the study period in all three GA groups were infant birth year and SGA (tables 4-6). For very and moderately preterm infants, maternal mental illness was also statistically significant in the adjusted analyses and also antenatal corticosteroids for moderately preterm infants (tables 5 and 6). How- ever, these factors only explained 0.5%, 2% and 13% of the decreasing trend in exclusive breastfeeding for moderately, very and extremely preterm infants, respectively. Furthermore, a low GA at birth also affected exclusive breastfeeding negatively (OR 1.14 CI 95% 1.14-1.15). However, the risks varied among the three gestational age groups. For extremely preterm infants, a lower GA did not affect exclusive breastfeeding (OR 0.96, 0.89-1.04), but for very (OR 1.17, 1.11-1.24) and moderately (OR 1.12, 1.1-1.15) preterm infants, a lower GA increased the risk for not breastfeeding exclusively.

34 Table 4. Unadjusted and adjusted logistic regression analyses for not breastfeeding exclusively at discharge from hospital in extremely preterm infants (GA 22-27 weeks, n=1 936), presented with odds ratios (ORs) and 95% confidence intervals (CIs). Data from the Swedish Neonatal Quality register from 2004-2013.

Percentage of infants exclusively breastfeed Unadjusted Adjusteda n (%) OR (95%CI) OR (95%) Infant birth year 1.28 (1.23-1.32) ** 1.27 (1.23-1.32) ** Maternal factors Maternal mental illness Yes 59 (3) 17% 1.98 (1.0-3.94) No 1 877 (97) 29% ref Preeclampsia Yes 240 (12) 33% 0.78 (0.59-1.05) No 1 696 (88) 28% ref Antenatal corticosteroids Yes 1 667 (86) 29% 0.80 (0.59-1.07) No 269 (14) 25% ref Caesarean section Yes 1 186 (61) 28% 1.11 (0.90-1.35) No 749 (39) 30% ref Infant factors Multiple birth Multiple 499 (26) 19% 2.04 (1.58-2.62) ** Singleton 1 437 (74) 32% ref Small for gestational age Yes 162 (8) 17% 2.09 (1.37-3.20) ** 1.95 (1.26-3.03) ** No 1 774 (92) 29% ref Bronchopulmonary dysplasia Yes 1 056 (55) 27% 1.21 (1.0-1.48) No 880 (45) 31% ref Retinopathy of prematurity Yes 917 (47) 28% 1.01 (0.83-1.23) No 1 019 (53) 28% ref Necrotizing enterocolitis Yes 132 (7) 12% 3.05 (1.79-5.19) ** No 1 804 (93) 30% ref aAdjusted for factors that negatively affected breastfeeding and which became more prevalent from 2004- 2013. These factors include small for gestational age and infant birth year. * p<0.05 ** p<0.01

35 Table 5. Unadjusted and adjusted logistic regression analyses for not breastfeeding exclusively at discharge from hospital in very preterm infants (GA 28-31 weeks, n=4 595), presented with odds ratios (ORs) and 95% confidence intervals (CIs). Data from the Swedish Neonatal Quality register from 2004- 2013.

Percentage of infants exclusively breastfeed Unadjusted Adjusteda n (%) OR (95% CI) OR (95% CI) Infant birth year 1.04 (1.02-1.07) ** 1.04 (1.02-1.06) ** Maternal factors Maternal mental illness Yes 153 (3) 25% 2.08 (1.44-3.02) ** 2.00 (1.38-2.91) ** No 4 442 (97) 41% ref Gestational diabetes Yes 65 (1) 34% 1.32 (0.79-2.21) No 4 530 (99) 40% ref Preeclampsia Yes 895 (20) 39% 1.08 (0.93-1.26) No 3 700 (80) 41% ref Antenatal corticosteroids Yes 3 464 (75) 40% 1.08 (0.94-1.24) No 1 131 (25) 42% ref Caesarean section Yes 3 143 (68) 37% 1.61 (1.42-1.82) ** No 1 449 (32) 48% ref Infant factors Multiple birth Multiple 1 310 (29) 29% 1.97 (1.72-2.26) ** Singleton 3 285 (71) 45% ref Small for gestational age Yes 502 (11) 31% 1.58 (1.29-1.93) ** 1.57 (1.29-1.92) ** No 4 093 (89) 41% ref Bronchopulmonary dysplasia Yes 307 (7) 31% 1.52 (1.18-1.95) ** No 4 288 (93) 41% ref Retinopathy of prematurity Yes 219 (5) 35% 1.25 (0.94-1.67) No 4 376 (95) 40% ref Necrotizing enterocolitis Yes 60 (1) 25% 2.04 (1.13-3.66) * No 4 535 (99) 40% ref aAdjusted for factors that negatively affected breastfeeding and which became more prevalent from 2004- 2013. These factors include maternal mental illness, small for gestational age and infant birth year.

* p<0.05 ** p<0.01

36 Table 6. Unadjusted and adjusted logistic regression analyses for not breastfeeding exclusively at discharge from hospital in moderately preterm infants (GA 32-36 weeks, n=22 914), presented with odds ratios (ORs) and 95% confidence intervals (CIs). Data from the Swedish Neonatal Quality register from 2004-2013.

Percentage of infants exclusively breastfeed Unadjusted Adjusteda n (%) OR (95% CI) OR (95% CI) Infant birth year 1.09 (1.08-1.10) ** 1.09 (1.07-1.09) ** Maternal factors Maternal mental illness Yes 828 (4) 43% 1.74 (1.51-2.00) ** 1.60 (1.39-1.84) ** No 22 086 (96) 57% ref Gestational diabetes Yes 483 (2) 48% 1.42 (1.18-1.70) ** No 22 431 (98) 57% ref Preeclampsia Yes 3 040 (13) 51% 1.32 (1.22-1.42) ** No 19 874 (87) 58% ref Antenatal corticosteroids Yes 9 428 (32) 50% 1.40 (1.31-1.49) ** 1.16 (1.08-1.26) ** No 20 017 (68) 58% ref Caesarean section Yes 10 079 (44) 49% 1.71 (1.62-1.80) ** No 12 802 (56) 62% ref Infant factors Multiple birth Multiple 5 361 (23) 37% 2.88 (2.70-3.07) ** Singleton 17 553 (77) 63% ref Small for gestational age Yes 1 621 (7) 46% 1.56 (1.41-1.73) ** 1.49 (1.34-1.65) ** No 21 293 (93) 57% ref aAdjusted for factors that negatively affected breastfeeding and which became more prevalent from 2004- 2013. These factors include maternal mental illness, antenatal corticosteroids, small for gestational age and infant birth year. As well as for gestational age in weeks. * p<0.05 ** p<0.01

37 Study II (paper 3-5) Participating mothers and infants In total, 493 mothers were randomised to the intervention group (n=231) and control group (n=262). Maternal and infant characteristics did not differ between the two groups (table 7). Five mothers were lost to follow-up (i.e., did not answer the telephone or return any questionnaire) at eight weeks after discharge, four in the intervention group and one in the control group, with a dropout rate of 1%. Seven mothers in each group were lost to follow-up at 6 months, with a dropout rate of 3%. Of the 281 mothers who accepted to receive the 12-month questionnaire, 229 (82%) returned the questionnaire, which represented 46% of the whole (n=493) study population. There were no significant differences between the intervention and control groups regarding the response rate to the questionnaire at eight weeks after discharge or at 6 and 12 months PNA (p=0.28, p=0.24, and p=0.33, respectively). Significantly fewer mothers with a lower educational level (p<0.001) and mothers with a birth country other than Sweden (p<0.001) returned the questionnaire at eight weeks after discharge and at 6 months PNA. Mothers who did not return the questionnaire at 12 months PNA were also significantly younger (p=0.02), had a lower educational level (p<0.001), or were not born in Sweden (p=0.003). A flowchart of included and excluded mothers is shown in figure 3.

Table 7. Characteristics of the participating mothers (n=493), their preterm infants (n=547) and the NI- CUs (n=6). Demographic variables Total Intervention Control n (%) n (%) n (%) Maternal variables Randomised 493 231 (47) 262 (53) Age, year; mean (SD) 30 (5.2) 31 (5.3) 30 (5.1) Maternal educational level Higher education 258 (52) 123 (53) 135 (52) Upper secondary school or less 235 (48) 108 (47) 127 (48) Primipara 278 (56) 122 (53) 156 (60) Mothers not born in Sweden 46 (9.3) 27 (12) 19 (7.3) Vaginal birth 277 (56) 125 (54) 152 (58) Quality of life (SF-36); mean (SD)0 Physical functioning 83.5 (17.1) 83.5 (17.4) 83.5 (17.0) Social functioning 72.4 (26.8) 73.2 (27.0) 71.6 (27.0) Bodily pain 58.7 (27.3) 60.2 (26.4) 57.3 (28.1) Vitality 45.7 (20.9) 47.7 (21.3) 43.9 (20.4) General health 79.7 (15.8) 80.0 (16.3) 79.5 (15.4) Emotional wellbeing 74.1 (17.6) 74.1 (17.4) 74.1 (17.8) Role physical health 34.6 (40.9) 38.2 (41.5) 31.3 (40.0) Role emotional problems 78.4 (36.7) 79.6 (35.7) 77.3 (37.6)

38 Infant variables Gestational age at birth, weeks; median (IQR) 34 (2) 34 (2) 34 (2) Gestational age <28 weeks 17 (3.4) 10 (4.3) 7 (2.7) Gestational age 28-31 weeks 62 (13) 30 (13) 32 (12) Gestational age 32-36 weeks 414 (84) 191 (83) 223 (85) Gestational age at discharge, weeks; median (IQR) 38 (2) 38 (2) 38 (2) Birthweight, gram; mean (SD) 2295 (638) 2262 (657) 2324 (621) Weight at discharge, gram; mean (SD) 2880 (473) 2904 (541) 2858 (403) Small for gestational age 43 (8.7) 21 (9.1) 22 (8.7) Male 275 (56) 138 (60) 137 (52) Multiple birth 52 (11) 21 (9.1) 31 (12) Length of stay, days; median (IQR) 23 (21) 24 (20) 23 (22) Neonatal illness# 18 (3.7) 11 (4.8) 7 (2.7) Breathing support¤ 233 (47) 108 (47) 125 (48) Domiciliary nursing care 448 (91) 212 (93) 236 (90) Domiciliary nursing care, days; median (IQR) 10 (12) 10 (11) 10 (12) Exclusive breastfeeding at discharge 406 (82) 184 (80) 222 (85) NICU 1 109 (22) 49 (21) 60 (23) NICU 2 74 (15) 34 (15) 40 (15) NICU 3 77 (16) 36 (16) 41 (16) NICU 4 94 (19) 44 (19) 50 (19) NICU 5 93 (19) 46 (20) 47 (18) NICU 6 46 (9.3) 22 (9.5) 24 (9.2) IQR = interquartile range, NICU = neonatal intensive care unit, SD = standard deviation 0 Measured at baseline. Missing data on SF-36 in 23 mothers # Bronchopulmonary dysplasia, Retinopathy of prematurity, Necrotizing enterocolitis, Intraventricular haemorrhage, Periventricular leukomalacia ¤Treatment with ventilator, continuous positive airway pressure or high flow oxygen

39 Figure 3. Flowchart of the randomisation, allocation and numbers analysed in study II.

40 Effects of proactive breastfeeding support

Effects of the intervention on breastfeeding and method of feeding There were no significant differences in the primary outcome, exclusive breastfeeding prevalence at eight weeks after discharge, between the intervention and control group, with an OR for not breastfeeding exclusively in the control group of 0.96 (CI 95% 0.66-1.38) (paper 3). There were no long-term effects of the intervention, with an OR for not breastfeeding exclusively in the control group at 6 months of 1.15 (0.74-1.79), and at 12 months PNA there was no statistically significant difference in partial breastfeeding between the groups (OR 0.86, CI 95% 0.45-1.62) (paper 4). Furthermore, there were no differences between the intervention and control group with respect to the risk for ceasing breastfeeding (log rank test p=0.68) and the method of feeding during the first 12 months PNA (paper 4).

Effects of proactive support on satisfaction with breastfeeding, attachment, parental stress and quality of life In paper 3, the results obtained for the secondary outcomes revealed no differences between the intervention and control group in terms of maternal satisfaction with breastfeeding, attachment or quality of life. However, intervention group mothers reported significantly less parental stress than the control group (t=2.44, 95% CI 0.03-0.23, effect size d=0.26). The dimensions role restriction and social isolation showed significantly lower scores in the intervention group compared with the control group (table 8).

41 Table 8. Differences between the intervention and control group on secondary outcome at eight weeks after discharge from the neonatal unit. Intervention Control eight Effect size eight weeks weeks Student's t-test Cohen's Mean (SD) Mean (SD) t (CI 95%) p-value d Maternal breastfeeding evaluation scale n=170 n=199 Total 113.7 (19.2) 113.6 (19.3) -0.04 (-4.05; 3.87) 0.97 0.004 Maternal enjoyment and role attainment 54.7 (10.6) 55.0 (10.6) 0.20 (-1.94; 2.39) 0.84 0.02 Infant satisfaction and growth 31.4 (6.4) 31.4 (6.0) -0.02 (-1.29; 1.26) 0.98 0.003 Lifestyle and maternal body image 27.6 (6.0) 27.3 (6.0) -0.48 (-1.52; 0.93) 0.63 0.05

Maternal postnatal attachment scale n=170 n=200 Global attachment score 83.7 (7.3) 83.6 (6.4) -0.23 (-1.56; 1.24) 0.82 0.02 Quality of bonding 41.5 (3.1) 41.2 (3.1) -0.89 (-0.92-3.35) 0.59 0.09 Absence of hostility 21.3 (2.7) 20.8 (2.5) -1.63 (-0.99-0.09) 0.37 0.19 Pleasure in Interaction 21.0 (3.3) 21.6 (3.1) 1.70 (-0.09-1.23) 0.09 -0.19

Swedish parental stress questionnaire n=170 n=200 Total 2.35 (0.50) 2.48 (0.51) 2.44 (0.03; 0.23) 0.015 0.26 Incompetence 1.94 (0.63) 2.06 (0.63) 1.86 (-0.01; 0.25) 0.64 0.19 Role restriction 3.44 (0.71) 3.61 (0.70) 2.38 (0.03; 0.32) 0.018 0.25 Social isolation 2.00 (0.63) 2.14 (0.65) 2.09 (0.01; 0.27) 0.037 0.22 Health problems 2.55 (0.65) 2.59 (0.69) 0.59 (-0.96; 0.18) 0.55 0.16 Spouse relationship problems 2.07 (0.82) 2.20 (0.86) 1.57 (-0.03; 0.31) 0.12 0.06

Quality of life (SF-36) n=170 n=201 Physical functioning 93.0 (10.3) 91.9 (11.9) -0.46 (-2.97; 1.85) 0.65 0.04 Social functioning 87.4 (18.4) 87.3 (19.1) -0.09 (-4.02; 3.67) 0.93 0.009 Bodily pain 83.2 (22.0) 84.5 (20.3) 0.62 (-2.97; 5.68) 0.54 0.06 Vitality 54.5 (21.1) 55.3 (19.4) 0.38 (-3.35; 4.95) 0.71 0.04 General health 79.1 (16.0) 77.9 (16.4) -0.73 (-4.56; 2.09) 0.47 0.08 Emotional wellbeing 78.9 (15.5) 79.0 (14.9) 0.08 (-2.98; 3.22) 0.94 0.007 Role-physical health 75.8 (35.6) 76.5 (35.3) 0.20 (-6.55; 7.99) 0.85 0.02 Role emotional problems 80.0 (36.9) 82.3 (33.5) 0.62 (-4.93; 9.45) 0.54 0.06

42 Breastfeeding and factors associated with the risk for ceasing breastfeeding In paper 4, the proportion of exclusive breastfeeding at discharge, eight weeks after discharge and 6 months PNA were 82% (n=406), 58% (n=282) and 23% (n=109), respectively. At 12 months, 21% (n=49) of the infants whose mothers responded to the questionnaire were partially breastfed. Among the participating mothers (who breastfed at discharge), no statistically significant differences were identified in the probability of ceasing breastfeeding during the first 12 months PNA related to the following: parity, mother’s birth country other than Sweden, mode of delivery, multiple births, GA at birth, SGA, length of stay or group allocation (paper 4). However, a lower maternal educational level, no domiciliary nursing care and partial breastfeeding at discharge increased the risk for ceasing breastfeeding during the first 12 months PNA in the unadjusted analysis. In the adjusted Cox regression analysis model, partial breastfeeding at discharge from the NICU, a lower maternal educational level and a longer length of stay increased the risk for ceasing breastfeeding during the first 12 months PNA (table 9).

43 Table 9. Risks for ceasing breastfeeding in unadjusted, adjusted and final model using Cox regression analyses with Hazard ratios (HRs) and 95% Confidence intervals (95%CIs) in 487 mothers of preterm infants. Unadjusted Adjusteda model Final model Variables HR (95%CI) p-value HR (95%) p-value HR (95%) p-value Maternal educational level Upper secondary school or less 1.42 (1.13-1.79) 0.003 1.49 (1.16-1.90) 0.002 1.42 (1.13-1.79) 0.003 Higher education ref ref ref Parity Primipara 1.06 (0.84-1.34) 0.63 1.11 (0.86-1.42) 0.43 Multiparous ref ref Mothers born in Sweden Yes 0.66 (0.42-1.06) 0.09 0.63 (0.38-1.04) 0.07 No ref ref Caesarean sectio Yes 1.01 (0.80-1.27) 0.95 1.14 (0.88-1.47) 0.31 No ref ref Multiple birth Yes 1.19 (0.84-1.67) 0.33 1.27 (0.88-1.84) 0.21 No ref ref Gestational age at birth (weeks) 1.02 (0.97-1.07) 0.44 0.99 (0.90-1.09) 0.84 Small for gestational age Yes 1.13 (0.78-1.66) 0.52 1.09 (0.72-1.63) 0.69 No ref ref Shorter length of stay (weeks) 0.98 (0.94-1.01) 0.20 0.95 (0.89-1.02) 0.17 0.96 (0.92-0.99) 0.019 Domiciliary nursing care No 1.54 (1.03-2.31) 0.04 1.41 (0.90-2.20) 0.13 Yes ref ref Breastfeeding at discharge Partial 1.61 (1.23-2.12) 0.001 1.70 (1.24-2.32) 0.001 1.81 (1.35-2.41) <0.001 Exclusive ref ref ref Randomised to Reactive group 1.04 (0.83-1.32) 0.71 1.05 (0.82-1.34) 0.69 Proactive group ref ref aAdjusted for all variables presented in model

44 As mentioned earlier, mothers who were partially breastfeeding at discharge had ceased breastfeeding more often than mothers who were exclusively breastfeeding eight weeks after discharge (OR 5.17, CI 95% 3.59-7.44), and an illustration of this observation is shown in figure 4. This difference was also statistically significant at 6 months PNA (OR 3.74, CI 95% 2.47-5.67). However, there were no differences in the cessation of breastfeeding between mothers who were exclusively or partially breastfeeding at discharge at 12 months PNA (OR 1.76, CI 95% 0.64-4.81).

Figure 4. Breastfeeding from discharge to eight weeks after discharge.

Method of feeding The results showed that most infants (85%) received breast milk directly at only the breast. Only two (0.4%) infants received exclusive breast milk by bottle at discharge. Less than 11% (n=52), 6% (n=27) and 1% (n=4) of the mothers who provided exclusive breast milk used a combination of bottle and breast at discharge, eight weeks after discharge and 6 months PNA, respectively. Less than 1% (n=10) of the infants received breast milk by tube or cup at discharge or later (table 10).

Table 10. Method of feeding breast milk at discharge (n=493), eight weeks after discharge (n=428), six months (n=308) and at 12 months (n=49) postnatal age. Breast in combination with Bottle and Only breast Only bottle Bottle Cup Tube cup Solid food n (%) n (%) n (%) n (%) n (%) n (%) n (%) Discharge Exclusive breast milk (n=406) 345 (85) 2 (0.5) 52 (13) 3 (0.7) 3 (0.7) 1 (0.2) 0 Partial breast milk (n=87) 0 7 (8) 78 (89) 2 (2) 0 0 0

Eight weeks after discharge Exclusive breast milk (n=281) 254 (90) 1 (0.4) 26 (9.5) 0 0 0 0 Partial breast milk (n=147) 0 2 (1) 145 (99) 0 0 0

Six months postnatal age Exclusive breast milk (n=109) 105 (96) 0 4 (4) 0 0 0 0 Partial breast milk (n=199) 0 0 112 (56) 0 0 0 87 (44)

12 months postnatal age Partial (n=49) 0 0 0 0 1 (2)* 0 48 (98) * Breast milk only by tube feeding

46 Mothers experiences of proactive and reactive support In paper 5 (study II), 365 mothers contributed data on their experiences of proactive (intervention) and reactive (control) support. Mothers in the intervention group were significantly more satisfied with the group allocation compared with mothers in the control group (98%, n=167 versus 88%, n=171, p<0.001). Of the 303 mothers who answered the questions on involvement and satisfaction with the breastfeeding support, the results showed that mothers in the intervention group were significantly more involved in the support (mean ± (SD) 8.6 (2.1) versus 7.2 (2.7), p<0.001) and satisfied with the support (8.8 (1.8) versus 7.5 (2.5), p<0.001) than those in the control group. Written qualitative data from 274 mothers and telephone interviews with 26 mothers were analysed and it emerged two global themes, “empowered by proactive support” and “duality of reactive support” (figure 5). Most mothers experienced the proactive and reactive support as positive and as good support; however, two weeks of support was experienced as too short. The mothers expressed a desire for fewer calls but over a longer period because they experienced later breastfeeding problems. The global theme “empowered by proactive support” included the organising theme strengthened mothering, which included encouragement and con- firmation from engaged staff in the breastfeeding support team. The mothers were also treated with respect and received feedback and individual support to their specific needs and situation. These techniques helped the mothers feel involved in the support process. In the other organising theme, supported by the teams’ knowledge and experience, the mothers acknowledged the breastfeeding support team’s special knowledge and experience with preterm infants and breastfeeding, which supported the mothers. The mothers saw the staff as knowledgeable and skilled and that the breastfeeding support team could answer the mothers’ questions, rendering trust. The last organising theme, feeling secure through continuity, meant that the mothers were relieved and grateful that someone called them regularly. They also expressed that they became calm knowing that they would receive a call during which they could ask questions or discuss problems. When the breastfeeding support team called, the mothers discussed minor problems that they did not discuss with anyone else. However, for some mothers with a negative experience of the NICU, proactive support was experienced as pressure to breastfeed and not being listened to. Most mothers did not use the reactive support. As they experienced well- functioning breastfeeding and sufficient support from family, their social network and/or health care. Furthermore, the mothers in the reactive group (control) experienced the support as dual. The global theme “duality of reactive support” included the organising theme having the opportunity, in which mothers felt secure by having a telephone number for professional support and stated that it was nice to have an opportunity to call for support. In the other

47 organising theme, serious enough issue to address?, the mothers described that they found it difficult to decide when to use the support. The mothers did not call for minor problems and pondered if the issue was serious enough to call for support. Some mothers did not call for support even though they had problems.

Figure 5. Thematic network, showing the organisation and global themes

48 Discussion

Summary of results The aim of this thesis was to describe the prevalence of breastfeeding in preterm infants and to evaluate the effectiveness and mothers’ experiences of a proactive person-centred telephone support programme after discharge. Fur- thermore, to describe the duration of breastfeeding and risks for ceasing breastfeeding up to 12 months. The results showed a declining breastfeeding prevalence among preterm infants in Sweden, especially in exclusive breastfeeding among extremely preterm infants. This decrease persisted despite adjustments for factors, which became more prevalent during the study period and negatively affected breastfeeding. Furthermore, there was no effect of the proactive breastfeeding support intervention on breastfeeding, maternal satisfaction with breastfeeding, attachment, quality of life and method of feeding up to 12 months PNA. However, parental stress was significantly lower in mothers who received proactive support. Mothers’ experienced empowerment by the proactive support and a duality in the reactive support. The results also showed that partial breastfeeding at discharge, a low maternal educational level and a longer length of stay increased the risk for ceasing breastfeeding during the first 12 months PNA.

Study I (paper 1) A substantial decline in the prevalence of exclusive breastfeeding at discharge has occurred for preterm infants between 2004 and 2013. The specific reasons for this decrease, especially in extremely preterm infants, are not known. The factors in the SNQ register that we adjusted for only explained 0.5%, 2% and 13% of the decrease in exclusive breastfeeding prevalence in moderately, very and extremely preterm infants, respectively. Our findings raise several concerns and pose challenges to neonatal units to support and promote breastfeeding. We can only speculate about potential factors that may have influenced the observed decline in breastfeeding. Hypothetically, four potential factors may affect this negative trend. First, fortification of breast milk has been increasingly practiced in Swedish neonatal units. Although these interventions are associated with improved short-term outcomes, such as better weight gain (96), there is limited evidence concerning long-term outcomes (97). Mothers

49 may doubt their breast milk quality if there is a great focus on breast milk content, millilitres and infant weight gain (50). Second, the staffing situation in Swedish neonatal units has changed during the study period from 2004- 2013 (98). With a high workload in the neonatal unit as well as many new staff members, lack of time and knowledge about breastfeeding may likely have affected the support given to mothers. A large body of research has shown that professional support is important for successful breastfeeding (99, 100). Third, although the physical environment is important for person-centred care (43), it could be argued that parents may be left to themselves in single-patient rooms, and that it may become more difficult for the staff to be present to support and promote breastfeeding compared to units with an open- bay room design. Fourth, there are indications that parents’ attitudes towards breastfeeding have changed during the past decades in Sweden. In one study, mothers experienced breastfeeding to be more difficult and reported more anx- iousness, tension and insecurity in 2011 than in 1992/1993 (101). The secondary findings in study II showed increased prevalence in factors that negatively affect breastfeeding. Mothers of preterm infants in Sweden were reported to have more physical and mental illnesses in 2013 than in 2004, of which many e.g., mental illness (102, 103), obesity (104) and gestational diabetes (105) negatively affect breastfeeding. The proportion of infants born SGA increased from 2004 to 2013, which is associated with a negative effect on exclusive breastfeeding. To our knowledge, the association between SGA and lower rates of breastfeeding has not been described previously and re- quires further investigation because of its important implications for infant health.

Study II (paper 2-5) There was no effect on the primary outcome of exclusive breastfeeding eight weeks after discharge or at any later follow-up during the first 12 months PNA. The lack of an effect of proactive telephone support on breastfeeding may depend on the relatively short intervention period (two weeks). Other proactive telephone interventions with a longer duration (up to two months) for full-term infants have had a positive effect on breastfeeding prevalence (106, 107). Furthermore, our qualitative data revealed a desire for support over a longer period because later breastfeeding problems occurred. Another possible explanation may be that many of these breastfeeding mothers had received domiciliary care for a period until discharge and may have received good support during the transition to home. It is possible that the intervention would have provided a significant improvement in breastfeeding in the intervention group in a context where domiciliary care was not practised in neonatal units.

50 There were no effects on secondary outcomes: maternal satisfaction with breastfeeding, attachment and quality of life by the intervention. However, parental stress was affected by the intervention; mothers who received proactive support reported significantly less parental stress. The total score obtained for the dimensions ‘role restriction’ and ‘social isolation’ were significantly lower in the intervention group. This is an important finding since parental stress affects the mother-infant relationship (108). This finding is consistent with the findings of our qualitative evaluation of mothers’ experiences of proactive and reactive support, which showed that when mothers received proactive support, they felt empowered. Empowerment has been shown to reduce stress and increase internal resources (109). Our hypothesis that proactive support could decrease parental stress was supported. Both the proactive and the reactive support had positive effects, i.e., the mothers felt secure, and during contact with the breastfeeding support team, they experienced the support as person-centred (i.e., being listened to with empathy, provided with information based on their needs and given encouragement and affirmation). The mothers who received proactive support felt significantly more involved with the support, and involvement is an important component of person-centred support (71, 84). This difference in involvement indicates that a proactive approach is important for providing person-centred care. A lack of involvement may increase the risk for inaccurate support. The intention in the trial was to deliver person-centred support and to do so by telephone. In McCormack’s (84) framework, four constructs are described from a ward or nursing home perspective. However, it seems possible to fulfil the four constructs through telephone support. In the trial, the prerequisites (characteristics of the support person) were met by recruiting staff within neonatal care who had knowledge of preterm infants and breastfeeding and to replenish their knowledge and educate them in person-centred support. The care environment (context) in this trial provided an advantage as the mothers were in their homes, a secure place for them. The disadvantage was that the mother and breastfeeding support team member did not see each other’s expressions or body language. There was a desire from some mothers for face- to-face contact. The person-centred process (delivering support) in this context seemed to work quite well, as the breastfeeding support team members were described as engaged, being there for the mother and providing individual support and affirmation. Expected outcomes (i.e., satisfaction with and involvement in the support and a feeling of well-being) were met for most mothers in the proactive group and for the mothers who contacted the breastfeeding support team. However, the mothers in the reactive group (control) felt less involved in the support compared with those in the proactive support. A proactive approach seems to be important for support to fulfil all components of person-centred support (71, 84). Furthermore, the findings from study II showed that, among mothers who breastfed their preterm infant at discharge, a low educational level increased

51 the risk for ceasing breastfeeding during the first 12 months PNA; these mothers were 42% more likely for ceasing breastfeeding compared with mothers with a high educational level. The cause of this association is unclear. A lower SES may predispose people by living habits that lead to illness, e.g., glucose intolerance and/or obesity and to biological effects influencing our health through changes in physiology (110). More mothers with glucose intolerance and obesity have shown delayed lactogenesis and/or a low milk supply compared with women with normal weight and glucose levels (111, 112). Another explanation may be that mothers with a lower educational level have less self- efficacy and/or less energy to persevere with breastfeeding due to less optimal resources, i.e., experience of stress, lack of family support and/or challenging social context (113, 114). Another risk factor for ceasing breastfeeding during the first 12 months PNA was partial breastfeeding at discharge from the NICU, with an 82% greater likelihood of ceasing breastfeeding. Health care staff should support early and continuous milk expression, addressing preterm infant feeding challenges, provide person-centred support to the mother, and acknowledge the importance of exclusive breastfeeding at discharge without creating pressure on the mother to breastfeed. Research has shown that breastfeeding directly at the breast is important for breastfeeding duration and that avoiding bottles facilitates breastfeeding (115, 116). In this study, most infants received breast milk directly at the breast, which is significantly different than, for example, the USA, Canada and Italy, where almost all infants receive breast milk through a combination of breast and bottle or only bottle (115, 117, 118). An additional risk factor in this study was a longer length of stay in the NICU, which increased the risk for ceasing breastfeeding during the infants’ first year of life, and for every additional week of stay, the risk for ceasing breastfeeding increased 4%. Mothers of preterm infants depend on milk expression, some- times for several months, to maintain breastfeeding, which may be a demanding task (46). Hypothetically, the long duration of milk expression in the neonatal unit may affect breastfeeding duration after discharge from the NICU and/or these infants may be more fragile or immature with more breastfeeding challenges such as infant illnesses, sleepiness or latching difficulties.

Strengths and limitations of the studies

Study I (paper 1) The main strength of paper 1 was that the SNQ register covers most preterm births in Sweden, and therefore the data can be considered representative of the country and thus provide good external validity in Sweden. Furthermore, the data were collected in a setting of standard clinical practice, and the study had a large sample size that enabled a better estimation of event rates; by

52 “hard” endpoints and outcomes, the external validity may be considered high. After exclusion of cases with missing data for breastfeeding (9.5%) at discharge and after checking the data variables we considered the data in the SNQ register to be reliable. A weakness of the study was that the SNQ registry had not been validated, which threatens the validity. The data on maternal mental illness were retrieved from a free text space in the questionnaires, and thus it is possible that not all mothers with a mental illness were disclosed resulting in an under-estimation of the prevalence of mental illness. Another weakness was that the SNQ register was not comprehensive from the start and did not include data on SES or mothers’ body mass index or smoking habits all of which are factors known to affect breastfeeding. Thus, the findings from the logistic regression analysis must be considered in relation to these limitations.

Study II (paper 2-5) The large study population, long-term follow-up and high response rate for the primary outcome (99%) strengthens the validity of the study. Furthermore, to our knowledge, this is the first trial to provide a telephone support intervention to mothers of preterm infants after discharge from a NICU. Moreover, the results are generalisable for Sweden as six NICUs participated and were geo- graphically spread across Sweden, comprising various care routines, environ- ments and NICU designs. Another strength of the RCT is that we used the intention-to-treat principle, which provides unbiased assessments of the treatment efficacy. There was also minimal loss to follow-up for the primary outcome and the eight-week and 6-month follow-ups. Blinding is an important methodological feature of RCTs to minimise bias and maximise the validity of the results. In study II, the researchers (i.e., Jenny Ericson, supervisors and statisticians) were blinded to the mothers’ group allocation until analyses of the primary outcome were performed. A major limitation was that although the recruitment period lasted 34 months, the trial was completed before reaching the calculated sample-size due to time constraints, which occurred because a smaller proportion of mothers breastfed at discharge than previously indicated (27, 82) and because of the number of mothers who declined to participate. Thus, this study was un- derpowered, which may threaten the internal validity. However, it seems un- likely that additional mothers would have changed the outcome of the intervention. Furthermore, the large block size (i.e., 25) provided an uneven distribution of mothers between the two randomisation groups, which could have affected the internal validity. However, there were no statistically significant differences between the intervention and control group for any maternal or infant characteristics. Another limitation was that the mothers who did not participate in the study or did not return the questionnaires were younger and had a

53 lower educational level than their counterparts, factors that are known to negatively influence breastfeeding (51, 119). Hence, mothers with the highest risk for early cessation participated to a lower extent, which affected the external validity, as mothers that were more vulnerable were not participating in the same extent as their counterparts. The Cox regression analyses of the duration and risk factors for ceasing breastfeeding are biased because only mothers who were breastfeeding at discharge were included in the study. Subsequently, the external validity was affected for generalisation of the results to all mothers of preterm infants. The instruments used to collect maternal satisfaction with breastfeeding, attachment, parental stress and quality of life were all validated with good psychometric properties. The instruments measuring parental stress and quality of life had been previously translated and validated in a Swedish context. The instruments measuring satisfaction with breastfeeding and attachment had not been translated and tested in Sweden prior to use in this study. None of the instruments has been applied to mothers of preterm infants, which is a weakness and may have affected the validity of the results due to the special situation of becoming a mother to a preterm infant with the increased stress, strains on the family and breastfeeding difficulties compared to mothers of infants born at term. However, all instruments had a high Cronbach’s alpha in this study, supporting a high reliability. In the evaluation of mothers’ experiences of the intervention, the large number of participating mothers and the mixed method approach should be considered as strengths. Using different methods to evaluate the experiences of mothers provide different perspectives and maternal experiences of proactive and reactive telephone support. Furthermore, the study includes experiences in both the intervention group and the control group, which is unusual in RCT studies, but very important. The main limitations with the mixed-method study were that the qualitative data originated from written open-ended questions and that interviews were conducted over the telephone instead of face-to-face. The depth and variation of the data might be limited. However, conducting telephone interviews and collecting written qualitative material enabled us to obtain data from a larger sample of mothers than would have been feasible with face-to-face interviews. Although the transferability to neonatal settings in other countries may be limited by the Swedish setting, the mothers’ experiences somewhat reflect the results from previous studies (71), strengthening the dependability and credi- bility of the study.

54 Conclusion

Breastfeeding prevalence has decreased from 2004 to 2013 among preterm infants in Sweden; this decline has remained significant despite adjustments for factors that negatively affect breastfeeding, which increased during the study period. The decline was most pronounced in exclusive breastfeeding among extremely preterm infants (<28 weeks GA). A proactive telephone support programme did not affect breastfeeding prevalence eight weeks after discharge or during the first 12 months PNA, nor did the intervention affect maternal breastfeeding satisfaction, attachment, quality of life or method of feeding. However, parental stress was significantly lower in mothers who received proactive support eight weeks after discharge. Thus, the provided proactive telephone support does not seem to affect breastfeeding, but it may be beneficial for reducing parental stress, which is important and should be investigated further. Mothers who received proactive support felt empowered and more satisfied and involved compared with mothers who received reactive support. Mothers who could only access reactive support experienced the support as dual in that they had access but hesitated to use it. These findings illuminate the importance of a proactive approach when supporting mothers of preterm infants after discharge. A low maternal educational level, partial breastfeeding at discharge and longer length of stay in the NICU were associated with an increased risk of cessation of breastfeeding during the first 12 months PNA. Most infants received breast milk directly from the breast, which is in contrast to the norm in other countries.

55 Future research and clinical implications

This thesis shows that breastfeeding prevalence is declining in preterm infants, especially exclusive breastfeeding among extremely preterm infants; this finding is worrying and must be acknowledged by neonatal units and society. Even small changes in prevalence affect infants’ health and health care costs (15). The reasons for the declining breastfeeding prevalence are unclear. Research should focus on exploring factors that potentially affect the negative trend in breastfeeding among preterm infants discharged from Swedish neonatal units. Changes in staffing, care routines, and the design of units may affect the prevalence and should be evaluated with respect to their effects on breastfeeding in future research. There is also a need to design and evaluate interventions that promote breastfeeding, as well as to implement current potentially beneficial interventions. As an example, research has shown that to optimally facilitate breastfeeding, support should be provided throughout the context of society, i.e., by increasing community awareness regarding breastfeeding, followed by support through the Baby Friendly Hospital Initiative (BFHI) and support counselling in the hospital, community and home (120). Furthermore, to facilitate breastfeeding at discharge from the neonatal unit, an area that may be improved is the implementation of early (within the first hour after birth) breastfeeding/milk expression, which has been shown to facilitate milk volume and breastfeeding at discharge from the neonatal unit in mothers of preterm infants (121, 122). Early initiation of breastfeeding is recommend by the World Health Organization (123). There is also a need to investigate the factors affecting the breastfeeding in mothers with a lower educational level. Hy- pothetically, both psychological and physiological factors may affect the difference in breastfeeding depending on the mothers’ educational level. Identi- fying these factors and understanding their roles are important for facilitating breastfeeding in mothers of preterm infants. The results from the RCT showed that the intervention had no effect on breastfeeding in this context. In future research, it would be interesting to evaluate proactive telephone support for a longer duration with fewer contacts in preterm infants and/or in a NICU context without domiciliary care or in full- term infants after discharge from postnatal wards. The positive result that proactive support affected parental stress should be further investigated because reduced parental stress facilitates the maternal-infant relationship, which is important for infant health and development.

56 Sammanfattning (in Swedish)

Syftet med denna avhandling var att undersöka amningsförekomst hos för tidigt födda barn (<37 graviditetsveckor, GV) samt utvärdera effekter av proaktivt personcentrerat telefonstöd efter utskrivning från neonatalavdelning. Vidare, att beskriva amningsduration och riskfaktorer för att sluta amma upp till 12 månader efter förlossningen. Amning och bröstmjölk ger hälsofördelar för barnet, till exempel ses förbättrade immunologiska, metaboliska och kog- nitiva funktioner. Bröstmjölk minskar även risken att drabbas av neonatala sjukdomar. För tidigt födda barn ammas dock i lägre utsträckning än barn födda i fullgången tid. Att bli mamma till ett barn som föds för tidigt och som vårdas på neonatalavdelning kan vara stressande och kan även påverka den känslomässiga processen att bli mamma. Första tiden hemma efter utskrivning från neonatalavdelning har av många mammor beskrivits som påfrestande med känslor som att vara ensam, brist på stöd och problem med amning. För att främja amning och mammans amningsupplevelse, anknytning, hälsa och minska stress, utformades och genomfördes en interventionsstudie. Vi undersökte om ett proaktivt personcentrerat telefonstöd de första 14 dagarna efter utskrivning från neonatalavdelning skulle öka andelen enbart ammande barn, mammans tillfredsställelse med amningen, anknytning till barnet, livskvalitet samt minska föräldrastress. Avhandlingen består av två studier som presenteras i fem delarbeten. Delarbete 1 (studie I) var en registerstudie med data från Svenskt neonatalt kvalitetsregister (SNQ). Studiegruppen bestod av 29 445 för tidigt födda barn födda 2004–2013 som skrevs ut till hemmet och hade amningsdata vid utskrivning. Resultaten visade att amningsfrekvensen minskade hos de för tidigt födda barnen mellan 2004 och 2013. Minskningen var signifikant för måttligt för tidigt födda (32-26 GV), mycket för tidigt födda barn (28-31 GV) men framför allt så hade andelen extremt för tidigt födda barn (<28 GV) som am- mades helt minskat, från 55 % år 2004 till 16 % år 2013. För samtliga grupper kvarstod minskningen trots justering för faktorer som påverkade amning negativt och hade ökat i prevalens under studieperioden. En faktor som både ökat i prevalens och påverkade amning negativt var barn som var små för tiden i alla tre åldersgrupper. Mammans psykiska ohälsa påverkade den negativa trenden i grupperna mycket och måttligt för tidigt född. Studie II är en interventionsstudie där delarbete 2 beskriver studiedesignen och genomförandet av en randomiserad kontrollerad multicenter studie om

57 proaktivt personcentrerat telefonstöd. Studien genomfördes på sex neona- talavdelningar i Sverige (Falun, Karlstad, Skövde, Sunderbyn, Trollhättan och Örebro). På varje avdelning fanns ett amningsstödjande team som rekryterade mammor och utförde interventionen. Mammorna lottades till en interventions- grupp med proaktivt stöd där mammorna blev uppringda en gång om dagen i 14 dagar efter utskrivning eller en kontrollgrupp som erhöll reaktivt stöd vilket innebar att mammorna själva fick ringa till amningsstödjande teamet om de hade frågor eller ville prata om något. Mammorna i interventionsgruppen kunde även använda det reaktiva stödet. Mammorna fick prata om vad de ville i kontakten med amningsstödjande teamet och mammor i interventionsgruppen kunde välja hur ofta och/eller när de ville bli uppringda. Totalt medver- kade 493 ammande mammor till för tidigt födda barn i studien. Studiens primära utfall presenteras i delarbete 3 och visade att det proaktiva personcentrerade telefonstödet inte påverkade helamning åtta veckor efter utskrivning från neonatalavdelningen, mammornas amningsupplevelse, anknytning och livskvalitet påverkades heller inte. Mammorna som erhöll proaktivt stöd hade dock en signifikant lägre föräldrastress jämfört med kontrollgrup- pen. I delarbete 4 visade resultaten att det proaktiva telefonstödet inte påverkade amningsfrekvensen eller metod för att ge barnet mat under det första året efter förlossningen. De flesta barn fick bröstmjölk via bröstet, få barn fick bröst- mjölk via nappflaska eller i en kombination med nappflaska, sond och/eller kopp. Vidare visade resultaten att delvis amning vid utskrivning, en låg ut- bildningsnivå hos mamman och en lång vårdtid på neonatalavdelningen var faktorer som ökade risken att sluta amma under det första året. I delarbete 5 användes en mixed-method approach med kvantitativa data från 365 mammor och med skriftliga kvalitativa data från 274 mammor samt telefonintervjuer med 26 mammor. Resultaten visade att mammor som erhöll proaktivt stöd var signifikant mer tillfredsställda och delaktiga i stödet jämfört med mammor som fått reaktivt stöd. Mammorna i den proaktiva gruppen upplevde att de fick kraft (empowered) av det proaktiva stödet, vilket innebar att de kände sig stärkta som mammor, upplevde stöd genom personalens kunskap och erfarenhet samt kände en säkerhet genom kontinuiteten i att bli uppringd varje dag. Mammorna som erhöll reaktivt stöd upplevde stödet som tudelat; det var tryggt att ha ett telefonnummer till amningsstödjande teamet på avdel- ningen samtidigt som de kände en tveksamhet om huruvida deras fråga var tillräckligt viktig att ringa för. Sammanfattningsvis har studierna visat att amningsprevalensen sjunker hos de för tidigt födda barnen vilket är oroande och en utmaning för samhället och sjukvården. Vilka faktorer som har påverkat den sjunkande amningstren- den är okända, men hypotetiskt kan faktorer som personalens kunskap och erfarenhet, personalomsättning och brist på tid för amningsstöd vara viktiga. Vidare har flertalet vårdrutiner förändrats under dessa 10 år, fler familjer vår- das på familjerum och det har även blivit ett ökat fokus barnets tillväxt med

58 till exempel beräkningsprogram för nutrition och tillväxt samt en ökad berik- ning av bröstmjölk, faktorer som troligen påverkar amningen. Resultaten från interventionsstudien visade att ett proaktivt telefonstöd inte påverkade amningsprevalens, amningsupplevelse, anknytning eller livskvalitet hos mammor med för tidigt födda barn under barnets första år. Orsaker till detta kan vara att stödet gavs under för kort tid och det är möjligt att stöd under en längre tidsperiod med glesare samtal skulle kunna ha varit mer effektivt. Mammorna kände sig dock stärkta av det proaktiva stödet och upplevde en lägre föräldrastress än mammor som enbart erhöll reaktivt stöd.

59 Acknowledgments

I would like to thank all those who have played an important role in my life during my PhD studies in various ways. Especially, I would like to thank the following:

Renée Flacking, my main supervisor and co-author. You have given me the best supervision one can get. You guided my through the design, implementation, statistics and interpretation. You always provided excellent points and input, in terms of both language and content. I have learned so much from you. A huge hug and a thousand thanks!

Mats Eriksson and Lena Hellström-Westas my assistant advisors and co- authors, thank you for the support and excellent input regarding the work we have done.

Pat Hoddinott, co-author, who always provided wise points and excellent input on our work.

Camilla Udo, co-author, who performed the telephone interviews and guided me in the qualitative world.

Lars Hagberg, co-author, who provided me insight regarding the quality of life scales and health economics.

The Centre for Clinical Research Dalarna, a fantastic work place and aca- demic environment with very nice people, thank you for your support and input to my work.

Department of Paediatrics, Falu Hospital, both to the neonatal unit who first supported this journey and the children’s ward who continued to support me.

My colleagues at the Department of Paediatrics, Falu Hospital, for their interest and support in my PhD studies.

60 The participating neonatal units, (Falun, Örebro, Sunderbyn, Trollhättan, Karlstad and Skövde) for their interest and support in the proactive breastfeeding support project.

The breastfeeding support team members, at each neonatal unit, for their engagement and excellent work in the study. Without their engagement, the study would not have been possible.

The participating mothers, you have my deepest gratitude for your participation and engagement in answering questionnaires and sharing your experiences.

Sverker Norlander, for invaluable IT-support and for being a very good rac- ing friend.

A special thanks to my mother Barbro Eriksson, father Leif Ericson, sister Anna Ericson and brother Kalle Ericson for their support during this time.

Most of all, I would like to thank my children Max, Olivia and William, for being who you are, for giving me the opportunity to be your mother and for the endless love I have for you.

The studies in this thesis were financially supported by: Centre for Clinical Research Dalarna Uppsala-Örebro Regional Research Council Gillbergska Foundation Birth Foundation Foundation Samariten The Swedish Nursing Association.

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69 Acta Universitatis Upsaliensis Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1398 Editor: The Dean of the Faculty of Medicine

A doctoral dissertation from the Faculty of Medicine, Uppsala University, is usually a summary of a number of papers. A few copies of the complete dissertation are kept at major Swedish research libraries, while the summary alone is distributed internationally through the series Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine. (Prior to January, 2005, the series was published under the title “Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine”.)

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