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  1. Mukherjee AP, Foong WC, Ferguson BR
    Med J Malaya, 1971 Jun;25(4):285-7.
    PMID: 4261302
  2. Foong SC, Tan ML, Foong WC, Ho JJ
    Arch Dis Child Educ Pract Ed, 2020 12;105(6):372-373.
    PMID: 31073039 DOI: 10.1136/archdischild-2018-316682
  3. Foong SC, Hwang YC, Foong WC, Tan ML
    Med J Malaysia, 2021 Nov;76(6):924-926.
    PMID: 34806687
    Methaemoglobinaemia occurs when there is >1% methaemoglobin in erythrocytes. In an infant, they can present either congenitally or in an acquired form. We present a rare case of methaemoglobinaemia presenting simultaneously in a mother and infant pair. The mother and infant were discharged well on Day-4 post-delivery with both mother and baby recording oxygen saturation levels of 100%. On Day-7, during a routine clinic visit, they were incidentally found to be centrally cyanosed. There were no other abnormalities. On investigation, the methaemoglobin levels were elevated in the infant (23.9%) and mother (14.3%). Treatment with ascorbic acid normalised mother's methaemoglobin levels; but baby's levels remained high until the administration of oral methylene blue. Both baby and mother remained well and pink at last follow-up at 2 years 8 months of age. This case illustrates difficulties in ascertaining the cause of methaemoglobinaemia. Postdelivery, the mother-neonate pair were pink, and their haemoglobin electrophoresis were normal, hence it was unlikely to be congenital methaemoglobinaemia. The team could not identify any triggering factors for acquired methaemoglobinaemia. There was also the uncertainty of the necessity to treat the baby. This is because treatment is not without harmful effects and despite the high methaemoglobin levels, the infant was otherwise well. Only a single published paper recommended that high methaemoglobin levels must be treated, and the recommendation was not supported by evidence. Lessons learnt from our case are that neonates with methaemoglobinaemia can be safely treated with oral methylene blue, but more research is needed on the benefitrisk profile of treatment.
  4. Lai NM, Foong SC, Foong WC, Tan K
    Cochrane Database Syst Rev, 2016 Apr 14;4(4):CD008313.
    PMID: 27075527 DOI: 10.1002/14651858.CD008313.pub3
    BACKGROUND: The increased birth rate of twins during recent decades and the improved prognosis of preterm infants have resulted in the need to explore measures that could optimize their growth and neurodevelopmental outcomes. It has been postulated that co-bedding simulates twins' intrauterine experiences in which co-regulatory behaviors between them are observed. These behaviors are proposed to benefit twins by reducing their stress, which may promote growth and development. However, in practice, uncertainty surrounds the benefit-risk profile of co-bedding.

    OBJECTIVES: We aimed to assess the effectiveness of co-bedding compared with separate (individual) care for stable preterm twins in the neonatal nursery in promoting growth and neurodevelopment and reducing short- and long-term morbidities, and to determine whether co-bedding is associated with significant adverse effects.As secondary objectives, we sought to evaluate effects of co-bedding via the following subgroup analyses: twin pairs with different weight ranges (very low birth weight [VLBW] < 1500 grams vs non-VLBW), twins with versus without significant growth discordance at birth, preterm versus borderline preterm twins, twins co-bedded in incubator versus cot at study entry, and twins randomized by twin pair versus neonatal unit.

    SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). We used keywords and medical subject headings (MeSH) to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (via PubMed), EMBASE (hosted by EBSCOHOST), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and references cited in our short-listed articles, up to February 29, 2016.

    SELECTION CRITERIA: We included randomized controlled trials with randomization by twin pair and/or by neonatal unit. We excluded cross-over studies.

    DATA COLLECTION AND ANALYSIS: We extracted data using standard methods of the CNRG. Two review authors independently assessed the relevance and risk of bias of retrieved records. We contacted the authors of included studies to request important information missing from their published papers. We expressed our results using risk ratios (RRs) and mean differences (MDs) when appropriate, along with 95% confidence intervals (95% CIs). We adjusted the unit of analysis from individual infants to twin pairs by averaging measurements for each twin pair (continuous outcomes) or by counting outcomes as positive if developed by either twin (dichotomous outcomes).

    MAIN RESULTS: Six studies met the inclusion criteria; however, only five studies provided data for analysis. Four of the six included studies were small and had significant limitations in design. As each study reported outcomes differently, data for most outcomes were effectively contributed by a single study. Study authors reported no differences between co-bedded twins and twins receiving separate care in terms of rate of weight gain (MD 0.20 grams/kg/d, 95% CI -1.60 to 2.00; one study; 18 pairs of twins; evidence of low quality); apnea, bradycardia, and desaturation (A/B/D) episodes (RR 0.85, 95% CI 0.18 to 4.05; one study; 62 pairs of twins; evidence of low quality); episodes in co-regulated states (MD 0.96, 95% CI -3.44 to 5.36; one study; three pairs of twins; evidence of very low quality); suspected or proven infection (RR 0.84, 95% CI 0.30 to 2.31; three studies; 65 pairs of twins; evidence of very low quality); length of hospital stay (MD -4.90 days, 95% CI -35.23 to 25.43; one study; three pairs of twins; evidence of very low quality); and parental satisfaction measured on a scale of 0 to 55 (MD -0.38, 95% CI -4.49 to 3.73; one study; nine pairs of twins; evidence of moderate quality). Although co-bedded twins appeared to have lower pain scores 30 seconds after heel lance on a scale of 0 to 21 (MD -0.96, 95% CI -1.68 to -0.23; two studies; 117 pairs of twins; I(2) = 75%; evidence of low quality), they had higher pain scores 90 seconds after the procedure (MD 1.00, 95% CI 0.14 to 1.86; one study; 62 pairs of twins). Substantial heterogeneity in the outcome of infant pain response after heel prick at 30 seconds post procedure and conflicting results at 30 and 90 seconds post procedure precluded clear conclusions.

    AUTHORS' CONCLUSIONS: Evidence on the benefits and harms of co-bedding for stable preterm twins was insufficient to permit recommendations for practice. Future studies must be adequately powered to detect clinically important differences in growth and neurodevelopment. Researchers should assess harms such as infection, along with medication errors and caregiver satisfaction.

  5. Foong WC, Loh CK, Ho JJ, Lau DS
    Cochrane Database Syst Rev, 2023 Jan 13;1(1):CD013767.
    PMID: 36637054 DOI: 10.1002/14651858.CD013767.pub2
    BACKGROUND: Non-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDβT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use.

    OBJECTIVES: To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDβT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer.

    SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 21 August 2022.

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer.

    DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDβT, quality of life and adverse events.

    MAIN RESULTS: We included seven RCTs involving 291 people with NTDβT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved. HbF inducer against placebo or usual care Three HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI -0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001. Adverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP. HbF inducer versus another HbF inducer Four studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence). Different doses of the same HbF inducer Two studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD -2.39 g/dL, 95% CI -2.80 to -1.98; very low-certainty evidence; HbF: MD -10.20%, 95% CI -16.28% to -4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects. A combination of HbF inducers versus a single HbF inducer Two studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported. Hydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD -0.74 g/dL, 95% CI -1.45 to -0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions. We are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group. None of the comparisons reported the outcome of HbF.

    AUTHORS' CONCLUSIONS: We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDβT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing.

  6. Foong WC, Ho JJ, Loh CK, Viprakasit V
    Cochrane Database Syst Rev, 2016 Oct 18;10(10):CD011579.
    PMID: 27755646
    BACKGROUND: Non-transfusion dependent beta thalassaemia is a subset of inherited haemoglobin disorders characterised by reduced production of the beta globin chain of the haemoglobin molecule leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it is required when episodes of chronic anaemia occur. This chronic anaemia can impair growth and affect quality of life. People with non-transfusion dependent beta thalassaemia suffer from iron overload due to their body's increased capability of absorbing iron from food sources. Iron overload becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin level have been found to require fewer blood transfusions. Hydroxyurea has been used to increase foetal haemoglobin level; however, its efficacy in reducing transfusion, chronic anaemia complications and its safety need to be established.

    OBJECTIVES: To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non-transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia).

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews.Date of last search: 30 April 2016.

    SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of hydroxyurea in people with non-transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea.

    DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments.

    MAIN RESULTS: No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks.Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference -2.39 (95% confidence interval - 2.8 to -1.98) and mean difference -1.5 (95% confidence interval -1.83 to -1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported.The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment.

    AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well-designed randomised controlled trials with sufficient duration of follow up are recommended.

  7. Tan ML, Foong SC, Ho JJ, Foong WC, Mohd R, Harun Z
    Int Breastfeed J, 2020 10 14;15(1):85.
    PMID: 33054789 DOI: 10.1186/s13006-020-00328-2
    BACKGROUND: Antenatal breastfeeding education (ANBE) is provided to all pregnant women attending Ministry of Health (MOH) clinics and some private health facilities in Malaysia, in line with the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). However, the 6 month exclusive breastfeeding prevalence remains relatively low in Malaysia, suggesting that there may be a gap between what is currently taught and what is received by the women.

    OBJECTIVES: To determine how women perceived their ANBE experience in the first 8 weeks postpartum including what was useful and what they would like to have been included, sources of ANBE and infant feeding practices at the time of survey.

    METHODS: Women during their first 8 weeks postpartum who attended MOH clinics in Penang State, Malaysia were surveyed using a self-administered questionnaire in April and May 2015. Categorical responses were presented as numbers and proportions while free text responses were compiled verbatim and categorised into themes. The perceptions of primiparous and multiparous women were compared. Multivariate logistic regression adjusted to known confounders was used to determine if ANBE was associated with exclusive breastfeeding at the time of survey.

    RESULTS: A total of 421 women completed the 15-item questionnaire (84% response rate) of which 282 were complete and available for analysis. Of these, 95% had received ANBE, majority (88%) from MOH clinics. Almost all women found it useful. However, there were areas both in the delivery (e.g. too short) and the content (e.g. nothing new) that were described as not useful; and areas they would like more coverage (e.g. milk expression, storage and overcoming low milk supply). The exclusive breastfeeding prevalence at the time of survey was 61%. ANBE was significantly associated with exclusive breastfeeding even after adjusting for confounders (adjusted odds ratio [aOR] 8.1, 95% confidence interval 1.7, 38.3).

    CONCLUSIONS: ANBE is widely implemented and perceived as useful and may be associated with exclusive breastfeeding. Our findings give insight into content that women would like more of and how delivery of ANBE could be improved, including individualized sessions and communicating at a suitable level and language. Future studies could focus on the quality of ANBE delivery.

  8. Foong SC, Tan ML, Foong WC, Ho JJ, Rahim FF
    Int Breastfeed J, 2021 01 06;16(1):4.
    PMID: 33407645 DOI: 10.1186/s13006-020-00353-1
    BACKGROUND: Ethnic Chinese mothers in Malaysia adhere to 30 days of traditional postpartum practices (the "confinement period") aimed at recuperation after delivery. Recently there has been an emergence of confinement centres (CCs) where mothers stay and receive traditional confinement care. Ethnic Chinese mothers have low breastfeeding rates. There are concerns that practices in CCs could contribute to this but no data exists. We described mothers' breastfeeding experiences at CCs and identified areas for potential improvement in breastfeeding support.

    METHODS: Ethnic Chinese mothers intending to breastfeed their healthy infants were recruited post-delivery between August and October 2017 then, at 1 and 6 months, they were telephone interviewed about their experience. For every participant going to a CC after the birth, another mother going home ("home") for her confinement was recruited. Chi-square test was used to compare groups and multiple logistic regression was used to assess the effect of confinement place on exclusive breastfeeding.

    RESULTS: Of 187 mothers, 88 (47%) went to CCs. Significantly more were primipara and fewer had previous breastfeeding experience. Response rates for the 1- and 6- month interviews were 88% (CC) versus 97% (home); and 77% (CC) versus 87% (home) respectively. Exclusive breastfeeding rates were similar between the groups: 62% (CC) versus 56% (home) at 1 month (p = 0.4); and 37% (CC) versus 42% (home) at 6 months (p = 0.5). Multiple logistic regression did not show that CCs were a factor affecting exclusive breastfeeding rates at 1 month, (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 0.9, 3.3), or 6 months (aOR 0.9, 95% CI 0.4, 1.7). However, significantly more CC participants only fed expressed breast milk. Despite 66% of CC participants reporting that their centre supported breastfeeding, only 6 (8%) CC participants compared to 66 (69%) of home participants roomed-in with their baby (p 

  9. Foong WC, Chean KY, Rahim FF, Goh AS, Yeoh SL, Yeoh AAC
    Health Qual Life Outcomes, 2022 Jan 08;20(1):2.
    PMID: 34998406 DOI: 10.1186/s12955-021-01897-4
    BACKGROUND: Improvement in medical management has enabled transfusion dependent thalassaemia (TDT) patients to survive beyond childhood, building families, and contributing to the labour force and society. Knowledge about their adult life would provide guidance on how to support their needs. This study aims to explore the general well-being of adults with TDT, their employment status and challenges.

    METHODS: This study recruited 450 people with TDT, aged 18 and above, of both genders through all regional Thalassaemia societies in Malaysia and from the two participating hospitals, over five months in year 2016. A self-administered questionnaire including 'Healthy Days Core Module', WHOQOL-BREF and employment measurements was used. Multiple linear regression models were fitted with associations adjusted for several potential confounders.

    RESULTS: A total of 196 adults with TDT responded to the survey (43.6% response rate). Almost half (45%) had comorbidities and 9% suffered multiple complications: bone-related (13%), hormonal (12%), cardiac (3%) and infections (2%), resulting in 23% seeking treatment more than twice monthly. Within a month, they suffered from at least three days with poor physical and or mental health and their normal daily activities were disrupted up to three days. 36% were jobless and 38% of those with a job were receiving salaries below RM1000. The mean WHOQOL-BREF score (mean (SD)) was: physical health 62.6 (15.5), psychological health 64.7 (15.7), social relationship 64 (15.9), environmental health 60.8 (16.7). Having days with mental issues, financial status, education level, ethnic and marital status were main factors affecting QOL scores. Open questions showed dissatisfaction with health service provision, conflicting judgement in prioritising between health and job, and poor public empathy.

    CONCLUSION: The adults with TDT perceived their health as good and had less unhealthy days when compared with people with other chronic diseases. However, some perceived themselves to be facing more life disruption in a rather non-supportive community and that health services do not meet their needs. Future qualitative studies are needed to focus on their perceived needs and to look for more tailored supportive approaches.

  10. Foong SC, Foong WC, Tan ML, Ho JJ, Omer-Salim A
    Int J Environ Res Public Health, 2022 Sep 01;19(17).
    PMID: 36078639 DOI: 10.3390/ijerph191710914
    With a focus on traditional practices rather than evidence-based practices, breastfeeding support is sub-optimal in confinement centres (CCs). We used a participatory, needs-based approach to develop a training module for CC staff adopting Kern's six-step approach as our conceptual framework. Of 46 identified CCs, 25 accepted our invitation to a dialogue aimed at establishing relationships and understanding their needs. An interactive training workshop was developed from the dialogue's findings. The workshop, attended by 32 CCs (101 participants), was conducted four times over a four-month period. Questions raised by the participants reflected deficits in understanding breastfeeding concepts and erroneous cultural beliefs. Correct answers rose from 20% pre-test to 51% post-test. Post-workshop feedback showed that participants appreciated the safe environment to ask questions, raise concerns and correct misconceptions. An interview conducted 14 months later showed that while some CCs improved breastfeeding support, others made no change due to conflict between breastfeeding and traditional postnatal practices, which was aggravated by a lack of support due to the COVID-19 pandemic. A participatory approach established a trustful learning environment, helping CCs appreciate the value of learning and adopting new concepts. However, cultural perceptions take time to change, hence continuous training and support are vital for sustained changes.
  11. Foong WC, Foong SC, Ho JJ, Gautam D, Leong JJ, Tan PY, et al.
    BMC Pregnancy Childbirth, 2023 Oct 03;23(1):706.
    PMID: 37789260 DOI: 10.1186/s12884-023-06021-6
    BACKGROUND: The updated World Health Organization (WHO) guideline recommends immediate kangaroo mother care (KMC) for all infants, particularly those born preterm. However, its uptake and sustainability have been unsatisfactory. Therefore, we aimed to gain deeper insight into factors influencing the uptake of KMC practice in our setting, and thereby identify possible solutions for the development of relevant interventions to improve its adoption and make KMC a routine practice for all infants.

    METHODS: Using the Triandis model of social behaviour as our framework, we conducted key informant interviews with parents and healthcare providers. Trained interviewers conducted interviews with nine parents, recruited via purposive sampling. These parents were parents of preterm infants who had been introduced to KMC. Data was transcribed and analysed based on Triandis' Theory of Interpersonal Behaviour. This paper only reports the results of the parent interviews.

    RESULTS: Major findings were how positive feelings like warmth and contentment, the sense of parenthood with KMC, the benefits of KMC for their infant and parents being enablers for KMC uptake. Conversely, the lack of KMC awareness, the initial negative feelings such as fear, uncertainty and embarrassment, the prioritization of time for milk expression, overcrowding in the ward, lack of space and privacy, limited visiting hours, lack of support and poor communication resulting in misapprehension about KMC were major barriers.

    CONCLUSION: A deeper understanding of the factors influencing the uptake of KMC using the Triandis behavioural model provided a way forward to help improve its uptake and sustainability in our settings.

    TRIAL REGISTRATION: This study was registered with the National Medical Research Registry (NMRR-17-2984-39191).

  12. Foong SC, Tan ML, Foong WC, Marasco LA, Ho JJ, Ong JH
    Cochrane Database Syst Rev, 2020 May 18;5(5):CD011505.
    PMID: 32421208 DOI: 10.1002/14651858.CD011505.pub2
    BACKGROUND: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use.

    OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs.

    SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019).

    SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials.

    DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification.

    MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome.

    AUTHORS' CONCLUSIONS: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.

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