Changes in unsettled infant sleep and maternal mood following admission to a parentcraft residential unit

BACKGROUND:: Maternal mood disorders are common in the first postnatal year, particularly if the infant has sleep problems. AIMS:: This study explored the effectiveness of a residential parentcraft unit's treatment for infant sleep problems, and also its impact on the mother's depression, anxiety, and bonding. STUDY DESIGN:: A one-group pretest-posttest design with follow-up was used. Assessments were conducted while participants were at the service, and at 5 weeks and 4 months after discharge. PARTICIPANTS:: Mothers (n=116) with infants 3 weeks to 3 years old presenting to a five-day program at an Australian residential parentcraft service because of unsettled infant sleep were recruited. OUTCOME MEASURES:: The Edinburgh Postnatal Depression Scale, the Hospital Anxiety and Depression Scale-Anxiety subscale (maternal mood), the Being a Mother & Bonding Scale (maternal experience and mother-infant bonding), and a Change Questionnaire (for infant sleep and maternal emotional health). RESULTS:: By 5 weeks post-discharge significant improvements were reported for infant sleep behavior, maternal mood (depressive and anxious symptoms), and maternal-infant bonding. 80% of the women reported an improvement on both their infants' sleep and their own emotional health, with strategies and support provided in the unit being cited by most women as the reason for improvement. Emotional health improvements were most often attributed to the improvement in the infant's sleep. All improvements by 5 weeks were maintained by the 4 four months assessment. CONCLUSION:: Where postnatal mood difficulties are reported along with unsettled infant sleep difficulties, the evidence from this uncontrolled study, together with previously research, suggests that treatment which principally focuses on the baby-care issue can have a significant impact on many women's emotional health.     

Early infant crying and sleeping problems: a pilot study of impact on parental well-being and parent-endorsed strategies for management

AIMS: Infant sleeping and crying problems are common and impact adversely on maternal mental health but their impact on paternal mental health is unknown. A consistent approach to managing such problems has not been identified. Parents may be able to identify useful management strategies, which could then inform the content of a prevention/early intervention approach to such problems. We aimed to determine the impact of infant behaviour problems on maternal and paternal mental health and management strategies that parents find useful. METHODS: Design: Pre-post intervention pilot. Setting: Paediatric outpatient clinic at the Royal Children's Hospital, Melbourne. Participants: 71 mothers and 60 fathers of infants aged 2 weeks to 7 months recruited from July 2004 to April 2005. Main outcome measures: Pre and post questionnaires measuring maternal and paternal well-being (Edinburgh Postnatal Depression Scale (EPDS)), parent report of infant behaviour problems, usefulness of consultation strategies. RESULTS: Three weeks post consultation, fewer parents reported that their infant's behaviour was still a problem (64% of mothers and 55% of fathers). Thirty per cent fewer mothers reported an EPDS score>12 (45% pre vs. 15% post clinic) while 11% fewer fathers reported an EPDS score>9 (30% pre vs. 19% post clinic). Most parents (80% or more) rated exclusion of medical causes and information about normal sleeping/crying as useful. CONCLUSIONS: Problem infant behaviours are associated with poor parental mental health. An intervention/prevention approach to infant behaviour problems should include fathers and contain information about normal infant sleeping and crying patterns and exclusion of medical causes.     

Improving infant sleep and maternal mental health: a cluster randomised trial.

OBJECTIVES: To determine whether a community-delivered intervention targeting infant sleep problems improves infant sleep and maternal well-being and to report the costs of this approach to the healthcare system. DESIGN: Cluster randomised trial. SETTING: 49 Maternal and Child Health (MCH) centres (clusters) in Melbourne, Australia. PARTICIPANTS: 328 mothers reporting an infant sleep problem at 7 months recruited during October-November 2003. INTERVENTION: Behavioural strategies delivered over individual structured MCH consultations versus usual care. MAIN OUTCOME MEASURES: Maternal report of infant sleep problem, depression symptoms (Edinburgh Postnatal Depression Scale (EPDS)), and SF-12 mental and physical health scores when infants were 10 and 12 months old. Costs included MCH sleep consultations, other healthcare services and intervention costs. RESULTS: Prevalence of infant sleep problems was lower in the intervention than control group at 10 months (56% vs 68%; adjusted OR 0.58 (95% CI: 0.36 to 0.94)) and 12 months (39% vs 55%; adjusted OR 0.50 (0.31 to 0.80)). EPDS scores indicated less depression at 10 months (adjusted mean difference -1.4 (-2.3 to -0.4) and 12 months (-1.7 (-2.6 to -0.7)). SF-12 mental health scores indicated better health at 10 months (adjusted mean difference 3.7 (1.5 to 5.8)) and 12 months (3.9 (1.8 to 6.1)). Total mean costs including intervention design, delivery and use of non-MCH nurse services were 96.93 pounds sterling and 116.79 pounds sterling per intervention and control family, respectively. CONCLUSIONS: Implementing this sleep intervention may lead to health gains for infants and mothers and resource savings for the healthcare system. TRIAL REGISTRATION: Current Controlled Trial Registry, number ISRCTN48752250 [controlled-trials.com] (registered November 2004).     

Maternal depression is associated with child undernutrition: A cross‐sectional study in Ethiopia

Child undernutrition is widespread in low‐ and middle‐income countries (LMIC) and is associated with health and economic losses. Undernutrition is estimated to contribute to 3.1 million deaths per year in children less than 5 years of age. A complex causal and contextual factors contributing to child undernutrition have been assessed, but maternal depression, which could contribute to child undernutrition by interfering with the mother's child caring practice and ability, has been received little attention. The objective of this study was to assess the association between maternal postpartum depression symptoms and infant (5–10 months of age) stunting in northern Ethiopia. A community‐based cross‐sectional study was conducted among mother–infant pairs (n = 232) between March and April 2018. Through interviewer‐administrated questionnaire, information on sociodemographic variables were collected, and maternal depression symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS≥13). Infants' length and weight were measured and converted to length and weight for age Z scores using the WHO growth standards. Breastfeeding was a norm, but the adequacy of complementary feeding practice was sub‐optimal. Only 25% of the infants met the minimum meal frequency (MMF), less than 10% met the minimum dietary diversity (MMD; 9%) or minimum acceptable diet (7%). Maternal depression was prevalent (22.8%) and was significantly associated with inappropriate complementary feeding and stunting (P < .05). Improving complementary feeding practices is central to preventing stunting in this and other settings. However, such efforts should integrate interventions that address maternal depression to improve child feeding and caring practices to effectively prevent stunting.     

Mood disorders among mothers of infants admitted to a mothercraft hospital

The mothers ( n = 100) of consecutive infants admitted to a mothercraft residential facility were asked to complete the Edinburgh Postnatal Depression Scale (EPDS). Only one of the women had been identified prior to the infant's admission as having postnatal depression, but 39% scored above the cut-off point for likely major depressive disorder. No specific infant problem correlated significantly with a higher depression score. The extent of serious mood disorders in the post-partum population has remained generally unacknowledged despite an upsurge of recent research activity in the field. Nevertheless, this problem has considerable public health significance, impinging as it does on the health of all members of the family. Possible screening and intervention strategies are discussed.     

Predictors of breastfeeding exclusivity among migrant and Canadian‐born women: results from a multi‐centre study

The objective of this study was to examine and compare predictors of breastfeeding exclusivity among migrant and Canadian‐born women. As part of a longitudinal study, a sample of 1184 mothers were recruited from 12 hospitals in Canada and completed questionnaires at 1 and 16 weeks post‐partum that included diverse questions from the following domains: demographic, social, migration, obstetrical, breastfeeding and maternal mood. After bivariate analysis, multivariate logistic regression analysis was completed to examine and compare predictors of exclusive breastfeeding at 16 weeks post‐partum. Among migrant women, factors predictive of breastfeeding exclusivity included non‐refugee immigrant or asylum‐seeking status, residence in Toronto or Vancouver, maternal age of ≥35 years, feels most comfortable in the country of origin or nowhere and higher Gender‐related Development Index of the country of origin. Factors predictive of not exclusively breastfeeding included maternal age of <20 years, not planning to exclusively breastfeed, not making the decision to breastfeed before pregnancy and not exclusively breastfeeding at 1 week post‐partum. Among Canadian‐born women, factors predictive of a lower likelihood of breastfeeding exclusivity included not living with father of infant, infant neonatal intensive care unit admission, planned duration of exclusive breastfeeding for <6 months, not exclusively breastfeeding at 1 week post‐partum and Edinburgh Postnatal Depression Scale score of ≥10. The only similar risk factor predicting a lower likelihood of breastfeeding exclusivity between migrant and Canadian‐born women was not exclusively breastfeeding at 1 week post‐partum; all other risk factors were dissimilar, suggesting that these groups might benefit from different strategies to optimise breastfeeding outcomes.     

Infantile colic, prolonged crying and maternal postnatal depression

Aim:  To study if infant crying is associated with maternal postnatal depression.
Methods:  Data from 1015 mothers and their children participating in a prospective European multicentre study were analysed. Infantile colic and prolonged crying were defined as excessive crying as reported by the mothers 2 and 6 months after delivery, and at the same time the mothers completed the Edinburgh Postnatal Depression Scale (EPDS).
Results:  In cross-sectional analyses, infant crying was associated with high EPDS scores both 2 (OR: 4.4; 95% CI: 2.4–8.2) and 6 months postpartum (OR: 10.8; 95% CI: 4.3–26.9). More than one-third of the others of infants with prolonged crying had high EPDS scores 6 months postpartum. Longitudinal analyses showed that mothers of infants with colic had increased odds of having high EPDS scores 6 months after delivery even if crying had resolved (OR: 3.7; 95% CI: 1.4–10.1).
Conclusion: Both infantile colic and prolonged crying were associated with high maternal depression scores. Most noteworthy, infantile colic at 2 months of age was associated with high maternal depression scores
4 months later.     

Factors determining HIV viral testing of infants in the context of mother‐to‐child transmission

Aim: The aim of this study was to investigate factors determining HIV viral testing of infants in the context of Prevention of Mother‐to‐Child Transmission of HIV (PMTCT). Methods: Post‐delivery HIV infected mothers 18 years and above with babies aged 3–6 months were interviewed on HIV viral testing of infants and factors associated with it. Results: Among 311 HIV infected women 61.7% had their infant tested for HIV between 4 and 8 weeks. Bivariate analyses found that older age of the mothers, lower depression scores, higher PMTCT knowledge, low PMTCT risk behaviour (maternal and infant nevirapine adherence, health facility delivery and exclusive formula feeding), HIV status disclosure and attending a support group were associated with PCR test participation. In multivariate analyses higher PMTCT knowledge, infant nevirapine adherence, and not exclusive breast feeding were associated with polymerase chain reaction test participation. Conclusion: Various determinants of acceptance of participation in HIV viral testing of infants in the context of PMTCT were identified that can guide infant testing and diagnosis counselling and support services of PMTCT programmes.     

Postnatal depression and infant growth and development in low income countries: a cohort study from Goa,India

Background: Postnatal depression is a recognised cause of delayed cognitive development in infants in developed countries. Being underweight is common in South Asia. Aims: To determine whether postnatal depression contributes to poor growth and development outcomes in Goa, India. Methods: Cohort study for growth outcomes with nested case-control study for developmental outcomes. A total of 171 babies were weighed and measured at 6–8 weeks following birth. The following measures were used: Edinburgh Postnatal Depression Scale for maternal mood, and sociodemographic and infant health variables. Outcome measures were: weight (<5th centile), length (<5th centile), and Developmental Assessment Scale for Indian Infants scores at six months. Results: Postnatal depression was a strong, and independent, predictor of low weight and length and was significantly associated with adverse mental development quotient scores. Conclusions: This study provides evidence for the first time that postnatal depression, a potentially treatable disorder, is a cause of poor growth and development in South Asia.     

The role of maternal depressed mood and behavioural soothing on infant response to routine vaccination

BACKGROUND: It has been hypothesized that maternal characteristics may affect infants' experience of pain during stressful medical procedures. AIM: To investigate the role of maternal depressed mood on infants' response to vaccination, and to determine the effectiveness of different soothing behaviours in reducing infant distress. METHODS: Twenty-eight mothers and their healthy, full-term infants participated in a prospective study. At infant age 2 mo, mothers completed the Edinburgh Postnatal Depression Scale (EPDS) and an adapted version of the Profile of Mood States (POMS); at infant age 4.5 mo, mothers were administered the mood scale and were observed with their infants during routine vaccination. RESULTS: Higher levels of maternal depressed mood were predictive of a stronger infant pain response at routine vaccination. Contingencies derived from sequential analyses revealed that the soothing behaviours most effective in reducing infant distress were holding and face-to-face contact, whereas looking at the child from a distance was significantly associated with an increase in infant distress. CONCLUSION: Our findings suggest that interventions to reduce infant pain during stressful medical procedures may include early detection and referral for maternal postpartum depression as well as the promotion of soothing behaviours involving close physical and emotional contact between mother and baby.     

Medicalizing normality? Management of irritability in babies

OBJECTIVE: The aims of this project were to identify the scources and quality of the health advice provided to parents with irritable infants; to assess the efficacy of a residential programme in the diagnosis and management of irritable infants; and to assess the intermediate term outcome for such infants and their mothers. METHODOLOGY: All mother-infant pairs admitted during a 3 month period to a residential setting with the primary concern of infant irritability were asked to participate in the study. Pre-admission and 3 month post-discharge health-care advice, investigations and treatment details were collected. Maternal mood at admission and 3 months post-discharge was measured using the Edinburgh Postnatal Depression Scale (EPDS). On admission, infant medication for proposed cause of excess irritability was ceased, with parental consent, if it was appropriate and following full medical assessment. Individual case plans were designed by the admitting child health nurse in consultation with the mother. These included education as to normal infant behaviour, settling techniques, and establishment of routine; family issues were also explored. RESULTS: Fifty-one consecutive mother-infant pairs consented to participate and formed the cohort, 48 (94%) were available for follow-up interview 3 months post-discharge. The average age on admission was 13 weeks (range 4-28 weeks), 32 (62.7%) were male, 34 (66.7%) were first born and 45 (88.2%) lived with both their parents. A multiplicity of health professionals had been involved in the pre-admission care, and 48 of the infants had been or were currently on medication for gastro-oesophageal reflux disease and or colic. At the end of admission, diagnoses made were predominantly behavioural (22) and feeding problems (20). Nine infants were felt to have an organic cause for their irritability. Maternal mood improved significantly on EPDS from the time of admission (45 (86.2%) of mothers with scores > or = 12, mean score 16.5) to post-admission follow up (9 (18. 8%) with scores > or = 12, mean score 7.2). CONCLUSIONS: There is evidence that a proportion of babies with 'normal' irritability are being incorrectly diagnosed as having an organic disorder exposing them inappropriately to medication, which may be harmful, and potentially creating lifelong problems for these infants and their families.     

Regional variations in prevalence of postpartum depressive symptoms: Population‐based survey

The purpose of the present study was to verify that there are regional variations in the detection rate of postpartum depressive symptoms in mothers. A population‐based survey of all women who gave birth in Fushimi Ward, Kyoto City during the period 1 December 2008–31 October 2010 was carried out. The Edinburgh Postnatal Depression Scale (EPDS) was completed by 2567 mothers of infants to measure postpartum depressive symptoms. The detection rate of postpartum depressive symptoms was compared between five localities. A significant difference was found between the lowest detection rate of postpartum depressive symptoms (8.4%) and the highest (18.1%; P < 0.001). A significant positive correlation was found between the proportion of houses in the locality receiving public assistance and the detection rate of postpartum depressive symptoms. The detection rate of postpartum depressive symptoms shows regional variations, suggesting a relationship with the poverty rate.     

Treating infant sleep disturbance: Does maternal mood impact upon effectiveness?

Aim:   To explore whether mild-to-moderate maternal depression affects the effectiveness of a behavioural approach to treating infant sleep disturbance (ISD).
Methods:   The health records of 90 mothers attending an inpatient parenting service for management of their 5–12-month-old infant's sleep difficulties were examined. These records contained detailed, nurse-completed, 24-hour behaviour charts of infant sleeping and crying. Participants were allocated to the depression group based on Edinburgh Depression Scale score and/or review of mental health assessment notes.
Results:   There were no differences between infants of mothers with ( n = 39) or without ( n = 51) depression on either (i) the severity of their initial sleeping difficulty, or (ii) their response to behavioural treatment. Both groups showed significant improvements over the 5-day stay on all sleep variables observed, including number of night wakings, time to fall asleep, time spent crying at night and total time slept at night.
Conclusions:   Mild-to-moderate maternal depression does not appear to attenuate ISD behavioural treatment outcomes. Given ISD treatment has been shown to improve maternal mood, the results of this study argue against recommendations initially to address maternal mood in isolation when managing ISD.     

Postnatal depression and infant growth and development in low income countries: a cohort study from Goa, India.

BACKGROUND: Postnatal depression is a recognised cause of delayed cognitive development in infants in developed countries. Being underweight is common in South Asia. AIMS: To determine whether postnatal depression contributes to poor growth and development outcomes in Goa, India. METHODS: Cohort study for growth outcomes with nested case-control study for developmental outcomes. A total of 171 babies were weighed and measured at 6-8 weeks following birth. The following measures were used: Edinburgh Postnatal Depression Scale for maternal mood, and sociodemographic and infant health variables. Outcome measures were: weight (<5th centile), length (<5th centile), and Developmental Assessment Scale for Indian Infants scores at six months. RESULTS: Postnatal depression was a strong, and independent, predictor of low weight and length and was significantly associated with adverse mental development quotient scores. CONCLUSIONS: This study provides evidence for the first time that postnatal depression, a potentially treatable disorder, is a cause of poor growth and development in South Asia.     

Parents,infants and health care: utilization of health services in the first 12 months of life

OBJECTIVE: To describe patterns of health-service use in the first 12 months of life. METHODS: In this prospective cohort study, 173 first-born infants and their families living in two middle socio-economic urban areas of Melbourne were enrolled consecutively when presenting for their initial maternal and child health nurse (MCHN) visit (at approximately 4 weeks of age). Families kept a daily "health diary" for the entire 12-month period, recording use of all health services for their infant, and reasons for the contact. RESULTS: There was an 87% completion rate of diaries. The mean number of visits to any health service, including medical, hospitals, MCHN services, pharmacists, allied health services and naturopaths, was 35.7 (95% CI 34.7-36.6) during the 12 months. Of these, 31% (mean 10.9 visits) were visits to a general practitioner (GP) and 41.5% (mean 14.3 visits) were visits to the MCHN. Infants' visits to the MCHN were far more frequent in the first 6 months of life compared with the second 6 months (10.3 vs 3.6, P < 0.001). Rates of GP use were constant over the same periods (5.3 vs 5.7, P = 0.8). CONCLUSIONS: In a universal health-care system, this high rate of health-service use equates to approximately one visit to a health service every 2 weeks in the first year of life. The majority of these visits appeared unrelated to illness. This previously undocumented data has implications for future integrated service delivery, health-professional training and policy development for this age group.     

Maternal mental health and infant dietary patterns in a statewide sample of Maryland WIC participants

The study's objective was to examine the relation between maternal mental health and infant dietary intake. A cross‐sectional, population‐based telephone survey was employed within a statewide sample of Maryland Special Supplemental Nutrition Program for Women, Infants and Children participants. A 24‐h diet recall was performed using the United States Department of Agriculture Automated Multiple‐Pass Method. Analyses presented were based on 689 mother–infant pairs. Overall, 36.5% of mothers reported introducing solids to their infants early (<4 months of age), and 40% reported adding cereal to their infant's bottle. Among 0–6‐month‐old infants, higher infant energy intake was associated with symptoms of maternal stress [β = 0.02; confidence interval (CI): 0.01, 0.04], depression (β = 0.04; CI: 0.01, 0.06) and overall maternal psychological distress (β = 0.02; CI: 0.003, 0.03). With early introduction of solids in the model, the significant associations between infant energy intake and maternal stress and maternal psychological distress became marginal (P‘s = 0.06–0.10). The association between infant energy intake and maternal depression remained significant (β = 0.03; CI: 0.01, 0.06). Among 4–6‐month‐old infants, intakes of breads and cereals were higher among mothers who reported more symptoms of stress (β = 0.12; CI: 0.04, 0.23), depression (β = 0.19; CI: 0.03, 0.34), anxiety (β = 0.15; CI: 0.02, 0.27) and overall psychological distress (β = 0.04; CI: 0.01, 0.07). Among 7–12‐month‐old infants, dietary intake was not related to mental health symptoms. Findings suggest poorer infant feeding practices and higher infant dietary intake during the first 6 months of age in the context of maternal mental health symptoms. Further research is needed to evaluate these effects on child dietary habits and growth patterns over time.     

Birth size and early pneumonia predict linear growth among HIV‐exposed uninfected infants

Stunting remains a global health priority, particularly in sub‐Saharan Africa. Identifying determinants of linear growth in HIV‐exposed uninfected (HEU) infants can inform interventions to prevent stunting in this vulnerable population. HIV‐infected mothers and their uninfected infants were followed monthly from pregnancy to 12‐month post‐partum in Nairobi, Kenya. Mixed‐effects models estimated the change in length‐for‐age z‐score (LAZ) from birth to 12 months by environmental, maternal, and infant characteristics. Multivariable models included factors univariately associated with LAZ. Among 372 HEU infants, mean LAZ decreased from ?0.54 (95% confidence interval [CI] [?0.67, ?0.41]) to ?1.09 (95% CI [?1.23, ?0.96]) between 0 and 12 months. Declines in LAZ were associated with crowding (≥2 persons per room; adjusted difference [AD] in 0–12 month change: ?0.46; 95% CI [?0.87, ?0.05]), use of a pit latrine versus a flush toilet (AD: ?0.29; 95% CI [?0.57, ?0.02]), and early infant pneumonia (AD: ?1.14; 95% CI [?1.99, ?0.29]). Infants with low birthweight (<2,500 g; AD: 1.08; 95% CI [0.40, 1.76]) and birth stunting (AD: 1.11; 95% CI [0.45, 1.78]) experienced improved linear growth. By 12 months of age, 46 infants were stunted, of whom 11 (24%) were stunted at birth. Of the 34 infants stunted at birth with an available 12‐month LAZ, 68% were not stunted at 12 months. Some low birthweight and birth‐stunted HEU infants had significant linear growth recovery. Early infant pneumonia and household environment predicted poor linear growth and may identify a subgroup of HEU infants for whom to provide growth‐promoting interventions.     

When separation is not the answer: Breastfeeding mothers and infants affected by COVID‐19

The World Health Organization (WHO) has provided detailed guidance on the care of infants of women who are persons under investigation (PUI) or confirmed to have COVID‐19. The guidance supports immediate post‐partum mother–infant contact and breastfeeding with appropriate respiratory precautions. Although many countries have followed WHO guidance, others have implemented infection prevention and control (IPC) policies that impose varying levels of post‐partum separation and discourage or prohibit breastfeeding or provision of expressed breast milk. These policies aim to protect infants from the potential harm of infection from their mothers, yet they may fail to fully account for the impact of separation. Global COVID‐19 data are suggestive of potentially lower susceptibility and a typically milder course of disease among children, although the potential for severe disease in infancy remains. Separation causes cumulative harms, including disrupting breastfeeding and limiting its protection against infectious disease, which has disproportionate impacts on vulnerable infants. Separation also presumes the replaceability of breastfeeding—a risk that is magnified in emergencies. Moreover, separation does not ensure lower viral exposure during hospitalizations and post‐discharge, and contributes to the burden on overwhelmed health systems. Finally, separation magnifies maternal health consequences of insufficient breastfeeding and compounds trauma in communities who have experienced long‐standing inequities and violence, including family separation. Taken together, separating PUI/confirmed SARS‐CoV‐2‐positive mothers and their infants may lead to excess preventable illnesses and deaths among infants and women around the world. Health services must consider the short‐andlong‐term impacts of separating mothers and infants in their policies.     

Effectiveness of an individualized multidisciplinary programme for managing unsettled infants

OBJECTIVE: To ascertain the effectiveness of an individualized multidisciplinary residential programme for managing young unsettled infants and whether changes in unsettled behaviour were maintained. METHODS: One hundred and nine clients of a Tresillian residential unit with singleton infants aged less than 20 weeks were studied before, during and after intervention. Mothers completed a 24 h infant activity record prior to admission, during the stay and 1 month after discharge. Intervention consisted of settling techniques, parent education, support and counselling. RESULTS: By day 4 of admission, the mean duration of unsettled (fussing, crying) behaviour had decreased significantly and mean sleeping time and awake/content times both increased significantly (P < 0.001). These changes were maintained 1 month after discharge. Changes in behaviour were particularly marked for very unsettled infants. CONCLUSIONS: In the absence of formal controls, the individualized programme appears effective in managing the behaviour of unsettled infants.