Effect of Kangaroo Mother Care in Low Birth Weight Infants on Breastfeeding Performance, Gut Function, and Maternal Depressive Symptoms in Low Middle Income Populations in the Indian Subcontinent

Matalan syntymäpainon (Low Birth Weight, LBW) omaavilla vastasyntyneillä on lisääntynyt riski kuolemaan ja sairauksiin, joilla on monia lyhyen ja pitkän aikavälin seurauksia. Maailman terveysjärjestön (World Health Organization, WHO) määrittelemänä kenguruhoito (Kangaroo Mother Care, kenguruhoito) on interventio, joka kattaa äidin ja vastasyntyneen välisen ihokontaktin yhdessä yksinomaisen imetyksen kanssa (1). WHO suosittelee kenguruhoidon harjoittamista LBW-vauvoilla. Tämä suositus perustuu näyttöön siitä, että kenguruhoito voi merkittävästi vähentää kuolemia ja ehkäistä sairauksia LBW-vauvoilla. Kenguruhoidon käyttöönotossa on kehitysmaissa kuitenkin raportoitu vastustusta ja sen arvioitu kattavuus on vielä alhainen. Tieto kenguruhoidon laajasta hyödystä puuttuu terveydenhuollon ammattilaisilta sekä yhteisöltä. Kenguruhoidon mahdolliset hyödyt ovat usein epäselviä myös äideille, mikä usein toimii esteenä sen käytön edistämiselle ja toteuttamiselle. Tämän väitöskirjatutkimuksessa arvioitiin kenguruhoidon edistämisen ja tuen vaikutusta tärkeisiin biologisiin päätetapahtumiin, kuten vastasyntyneen rintaruokintakäyttäytymiseen (Tutkimus I), vastasyntyneen suolistofunktion biomarkkereihin (Tutkimus II) ja äidin synnytyksenjälkeisiin masennusoireisiin (Tutkimus III). Hypoteesi oli, että kenguruhoito voi parantaa vastasyntyneen rintaruokintakäyttäytymistä ja vähentää äidin synnytyksenjälkeisten masennusoireiden riskiä parantamalla äidin ja vastasyntyneen välistä vuorovaikutusta sekä edistämällä vastasyntyneen suolistofunktiota ja vähentämällä lapsen altistumista patogeeneille. Väitöskirjatutkimukset suunniteltiin osaksi suurempaa kliinistä hoitokoetta, jossa testattiin voiko kotona aloitetulla kenguruhoidon vähentää vastasyntyneitten kuolleisuutta ja muutoin edistää heidän ja heidän äitiensä terveyttä. Tutkimus toteutettiin Haryanan maaseutualueilla Pohjois-Intiassa, huhtikuun 2017 ja maaliskuun 2018 välisenä aikana. Tutkimuksen osallistujat olivat hyväkuntoisia, yksisikiöisestä rastaudesta syntyneitä vastasyntyneitä, joiden syntymäpaino oli 1500– 2250 grammaa, joille ei aiemmin oltu aloitettu kenguruhoitoa. Interventio sisälsi varhaisen ihokontaktin edistämisen syntymän jälkeen ja imetyksen tukemisen yksinomaisen rintaruokinnan edistämiseksi. Interventiotiimi teki kotikäynnin interventioryhmän perheiden luokse 1, 2, 3, 5, 7, 10, 14, 21 ja 28 päivää syntymän jälkeen. Näillä kotikäynneillä tarkkailtiin ihokontaktin ja imetyksen harjoittamista, ja tiimi auttoi äitiä ratkaisemaan mahdolliset vaikeudet kenguruhoidon toteutuksessa. Kontrolliperheille ei tehty näitä kotikäyntejä. Sekä interventio- ja kontrolliryhmien vastasyntyneille tarjottiin tavanomaiset perusterveydenhuollon palvelut, mukaan lukien kotona tapahtuvat vastasyntyneiden hoitokäynnit, jotka kuuluivat julkisen terveysjärjestelmän terveydenhuollon työntekijöiden tehtäviksi. Tutkimuksen päätetapahtumien arviointi tapahtui itsenäisten ja koulutettujen tiimien toimesta. Vauvojen rintaruokintakäyttäytymistä arvioitiin käyttämällä validoitua "vastasyntyneen imetyksen arviointityökalua" (IBFAT) vastasyntyneisyyskauden lopussa. Tehokas rintaruokintakäyttäytyminen määriteltiin IBFAT-pistemääräksi, joka oli suurempi tai yhtä suuri kuin 10. Suoliston toiminnan arvioimiseksi kerättiin vastasyntyneiden ulostenäytteitä. Ulosteen biomarkkereiden, kuten neopteriinin, myeloperoksidaasin ja alfa-1-antitrypsiinin pitoisuudet, arvioitiin automatisoidulla ELISA-järjestelmällä vastasyntyneisyyskauden lopussa. Äidin synnytyksenjälkeisten masennusoireiden arvioimiseen käytettiin validoitua "Potilaan terveyskyselylomaketta-9" (PHQ-9) 28 päivän kuluttua synnytyksestä. Kohtalaiset tai vaikeat synnytyksenjälkeiset masennusoireet määriteltiin PHQ-9-pistemääräksi, joka oli suurempi tai yhtä suuri kuin 10. Tutkimuksessa I oli 550 osallistujaa, joista tiedot päätetapahtumista olivat käytössä 98 %:ssa interventioryhmästä ja 95 %:ssa kontrolliryhmästä. Tutkimuksessa II oli 200 osallistujaa ja heistä ulosteen biomarkkereiden arvioinnit suoritettiin 99 – 100 %:lle sekä interventio- että kontrolliryhmässä. Tutkimuksessa III oli 1950 äitiä ja heistä tiedot masennusoireista selvitettiin 93 %:lta interventioryhmässä ja 94 %:lta kontrolliryhmässä. Tutkimuksessa I tehokas rintaruokintakäyttäytyminen havaittiin 92 %:lla (232/252) interventioryhmän vastasyntyneistä ja 81 %:lla (223/276) kontrolliryhmän vastasyntyneistä. Mahdollisten sekottavien tekijöiden suhteen vakioitu esiintyvyyssuhde (95 %:n luottamusväli) tehokkaalle rintaruokintakäyttäytymiselle oli 1,24 (1,16 - 1,32), mikä vastaa 24 %: vaikutusta (16 - 32 %). Tutkimuksessa II interventio- ja kontrolliryhmän osallistujien välillä korjattu ero logaritmisesti muunnetussa neopteriinin pitoisuudessa oli 0,03 (95 %:n luottamusväli -0,15 - +0,21), myeloperoksidaasissa 0,28 (95 %:n luottamusväli -0,05 - 0,61) ja alfa-1-antitrypsiinissä 0,02 (95 %:n luottamusväli -0,30 - 0,34). Ulosten biomarkkerien pitoisuuksissa ei siis havaittu tilastollisesti merkitseviä eroja interventioryhmän ja kontrolliryhmän lasten välillä. Tutkimuksessa III kohtalaisia tai vaikeita synnytyksenjälkeisiä masennusoireita kirjattiin 10,8 %:lla äideistä interventioryhmässä ja 13,6 %:lla äideistä kontrolliryhmässä. Vakioitu suhteellinen riski (95 %:n luottamusväli) kohtalaisille ja vaikeille synnytyksenjälkeisille masennusoireille oli interventioryhmän äideillä 0,75 (0,59 - 0,96). Tästä laskettuna interventio vähensi keskivaikeiden tai vaikeiden masennusoireitten esiintyvyyttä 25 % (4 % - 41 %). Tulokset osoittivat, että Haryanan Pohjois-Intian alueen matalan keskitulotason alueilla kenguruhoidon edistäminen ja tukeminen hyväkuntoisten matalan syntymäpainon omaavien vauvojen kohdalla voi merkittävästi parantaa vastasyntyneiden rintaruokintakäyttäytymistä, vähentää äitien synnytyksenjälkeisten kohtalaisten ja vaikeiden masennusoireiden riskiä, mutta sillä ei ole merkittävää vaikutusta valittujen biomarkkeireiden pitoisuuksiin lasten ulosteessa vastasyntyneisyyskauden lopussa. Tulokset tukevat kenguruhoidon edistämistä julkisen terveydenhuollon ohjelmissa Intian matalan keskitulotason väestöissä ja vastaavissa Etelä-Aasian maissa. Jatkossa olisi hyvä selvittää kenguruhoidon teho sairailla tai erittäin matalan syntymäpainon omaavilla vastasyntyneillä sekä sen pitkäaikaisvaikutukset sekä lasten että äitien terveyteen.Infants born low birth weight (LBW) have an increased risk of death and illness with many short-term and long-term consequences. As defined by the World Health Organization (WHO), Kangaroo Mother Care (KMC) is an intervention encompassing skin-to-skin-contact between the mother and the infant along with exclusive breastfeeding (1). The WHO recommends practice of KMC in LBW infants. This recommendation is based on the evidence that KMC can substantially reduce deaths and prevent morbidities in LBW infants. Despite the WHO recommendations, there has been reports of resistance towards implementing KMC in developing countries and the estimated coverage of KMC is low. Knowledge on the wide range of benefits of KMC is lacking amongst health care practitioners as well as in the community. Moreover, the potential benefits of KMC to the mothers is unclear, which often presents as a barrier to its promotion and practice. The PhD studies were therefore designed to assess the effect of promotion and support of KMC on some important biological outcomes i.e., infant breastfeeding performance (Study I), biomarkers of infant gut function (Study II), and maternal postpartum depressive symptoms (Study III). The hypothesis was that KMC can improve infant breastfeeding performance and reduce the risk of maternal postpartum depressive symptoms through enhanced mother-infant bonding and improve infant gut function through reduced pathogen exposure. The PhD studies were designed as randomized controlled trials embedded within the larger primary KMC trial titled “Impact of Community-initiated Kangaroo Mother Care on Survival of Low Birth Weight Infants” conducted in rural areas of Haryana, North India. Enrolment in the PhD studies were done between April 2017 to March 2018. In the PhD studies, we enrolled stable singleton LBW infants weighing between ≥1500 to ≤2250 grams within 72 hours of birth, born at home, or at hospital with KMC not initiated. The intervention included promotion and support for early skin-to-skin contact after birth and lactation management to promote exclusive breastfeeding. The intervention delivery team conducted scheduled visits to the homes of the families on 1, 2, 3, 5, 7, 10, 14, 21, and 28 days after birth. During these home visits, practice of skin-to-skin-contact and breastfeeding were observed. The team helped to resolve any difficulties related to KMC practice. Infants in the intervention and control arms of the trial received standard of care i.e., home-based newborn care visits delivered by the health workers of the government health system. Outcome assessments in the PhD studies were conducted by independent and trained teams. Infant breastfeeding performance was assessed using the validated ‘infant breastfeeding assessment tool’ (IBFAT) at the end of the neonatal period. Effective breastfeeding performance was defined by a IBFAT score of more than or equal to 10. For assessment of gut function, infant stool specimens were collected. Concentration of the fecal biomarkers neopterin, myeloperoxidase, and alpha-1- antitrypsin, were assessed using an automated ELISA system at the end of the neonatal period. The validated ‘Patient Health Questionnaire-9’ (PHQ-9) was used to assess maternal postpartum depressive symptoms at 28 days after birth. Moderate to severe postpartum depressive symptoms was defined by a PHQ-9 score of ≥10. In Study I, among the 550 enrolled participants, outcome assessments were completed in 98% in the intervention arm and 95% in the control arm. In Study II, among the 200 enrolled participants, assessments of fecal biomarkers were completed in 99% to 100% of the infants in both intervention and control arms. In Study III, among the 1950 enrolled participants, assessments were completed in 93% in the intervention arm, and 94% in the control arm. In Study I, effective breastfeeding performance was observed in 92% (232/252) of the infants in the intervention arm and 81% (223/276) of the infants in the control arm. The adjusted prevalence ratio (95% CI) for effective breastfeeding performance was 1.24 (1.16 to 1.32), corresponding to an effect of 24% (16 to 32%). In Study II, between the intervention arm and control arm participants, the adjusted difference in means in the log-transformed concentration of fecal neopterin was 0.03 (95% CI -0.15 to 0.21), myeloperoxidase was 0.28 (95% CI -0.05 to 0.61), and alpha-1-antitrypsin was 0.02 (95% CI -0.30 to 0.34. There was no substantial difference observed in any of the measured fecal biomarkers. In Study III, moderate-to-severe postpartum depressive symptoms were recorded among 10.8% of the mothers in the intervention arm against 13.6% of the mothers in the control arm. The adjusted relative risk (95% CI) for moderate-to-severe postpartum depressive symptoms was 0.75 (0.59 to 0.96). The corresponding efficacy of the intervention was 25% (4% to 41%). In conclusion, the findings showed that in low-middle income neighbourhoods in Haryana, North India, promotion and support of KMC in stable LBW infants can substantially improve infant breastfeeding performance, reduce the risk of maternal moderate-to-severe postpartum depressive symptoms, but does not have any substantial effect on the measured fecal biomarkers of infant gut function at the end of the neonatal period. The results support promotion of KMC in public health programs in low-middle income populations in India and in similar South Asian countries. Further research to study the effect of KMC in unstable or very low birth weight infants and its long-term effect on maternal and child health outcomes could be useful

Optimal breastfeeding practices and infant and child mortality: A systematic review and meta-analysis

Aim: To synthesise the evidence for effects of optimal breastfeeding on all-cause and infection-related mortality in infants and children aged 0–23 months. Methods: We conducted a systematic review to compare the effect of predominant, partial or nonbreastfeeding versus exclusive breastfeeding on mortality rates in the first six months of life and effect of no versus any breastfeeding on mortality rates between 6 and 23 months of age. A systematic literature search was conducted in PubMed, Cochrane CENTRAL and CABI. Results: The risk of all-cause mortality was higher in predominantly (RR 1.5), partially (RR 4.8) and nonbreastfed (RR14.4) infants compared to exclusively breastfed infants 0– 5 months of age. Children 6–11 and 12–23 months of age who were not breastfed had 1.8- and 2.0-fold higher risk of mortality, respectively, when compared to those who were breastfed. Risk of infection-related mortality in 0–5 months was higher in predominantly (RR 1.7), partially (RR 4.56) and nonbreastfed (RR 8.66) infants compared to exclusive breastfed infants. The risk was twofold higher in nonbreastfed children when compared to breastfed children aged 6–23 months. Conclusion: The findings underscore the importance of optimal breastfeeding practices during infancy and early childhood.publishedVersio

Genetic divergence studies for yield and its component traits in Mung bean (Vigna radiata L. Wilczek)

The present investigation was carried out at Genetics and Plant Breeding (GPB) farm, College of Agriculture, Central Agricultural University, Imphal, Manipur during kharif 2021 using 60 genotypes of Mung bean. Mahalanobis D2 statistics was used to evaluate the diversity. A total of fourteen clusters were formed with maximum number of genotypes in cluster I i.e., 29 genotypes followed by cluster II with 17 genotypes, cluster XII with 3 genotypes, all the remaining clusters were mono genotypic. It was found that the pattern of genotype distribution into different clusters was random and unrelated to geographic diversity. Results on genotype diversity between clusters IV and IX revealed the greatest inter-cluster distances, whereas cluster XII had the greatest intra-cluster distances. The largest cluster mean for seed yield per plant was found in cluster IX. Further, maximum contribution towards divergence was by number of seeds per plant (52.49%) followed by seed yield (17.8%) and days to 50% flowering (7.34%), while minimum by pod length which had shown 0% contribution

Enteral Calcium or Phosphorus Supplementation in Preterm or Low Birth Weight Infants: a Systematic Review and Meta-analysis

OBJECTIVES To assess effects of calcium or phosphorous supplementation compared with no supplementation in human milk-fed preterm or low birth weight infants. METHODS Data sources include Cochrane Central Register of Controlled Trials, Medline and Embase. We included Randomized controlled trials (RCTs) and non-randomized trials (quasi-randomized). RESULTS Three studies (4 reports; 162 infants) were included. At latest follow-up (38 weeks), there was reduction in osteopenia (3 studies, 159 participants, relative risk 0.68, 95% confidence interval [CI] 0.46–0.99). At latest follow-up (6 weeks), there was no effect on weight (1 study, 40 participants, mean difference [MD] 138.50 g, 95% CI −82.16 to 359.16); length (1 study, 40 participants, MD 0.77 cm, 95% CI −0.93 to 2.47); and head circumference (1 study, 40 participants, MD 0.33 cm, 95% CI −0.30 to 0.96). At latest follow-up, there was no effect on alkaline phosphatase (55 weeks) (2 studies, 122 participants, MD −126.11 IU/L, 95% CI −298.5 to 46.27, I2 = 73.4%); serum calcium (6 weeks) (1 study, 40 participants, MD 0.54 mg/dL, 95% CI −0.19 to 1.27); and serum phosphorus (6 weeks) (1 study, 40 participants, MD 0.07 mg/dL, 95% CI −0.22 to 0.36). The certainty of evidence ranged from very low to low. No studies reported on mortality and neurodevelopment outcomes. CONCLUSIONS The evidence is insufficient to determine whether enteral supplementation with calcium or phosphorus for preterm or low birth weight infants who are fed mother's own milk or donor human milk is associated with benefit or harm.publishedVersio

Effect of community-initiated kangaroo mother care on breastfeeding performance in low birthweight infants : A randomized clinical trial

This individually randomized trial was conducted to estimate the effect of promoting community-initiated kangaroo mother care (ciKMC) in low birthweight (LBW) infants on infant breastfeeding performance. It was designed as a substudy within a larger primary trial on ciKMC and infant survival. Five hundred fifty stable LBW mother-infant dyads (1500−2250 g) who provided consent, were consecutively enroled for breastfeeding performance assessment. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding (EBF) through home visits during the neonatal period. The primary outcome was effective breastfeeding performance indicated by an infant breastfeeding assessment tool score of ≥10 after the end of the neonatal period. As secondary outcomes, we reported maternal satisfaction related to infant breastfeeding, and EBF after the end of the neonatal period. We completed outcome assessments in 96% of participants. In the ciKMC arm, 92% of the infants showed effective breastfeeding performance against 81% in the control arm [adjusted prevalence ratio (aPR): 1.24, 95% confidence interval (CI): 1.16−1.32]. In the ciKMC arm, 65% of the mothers reported to be very satisfied with their infants' breastfeeding against 51% in the control arm (aPR: 1.22, 95% CI: 1.05−1.41). The proportion of infants practicing EBF was 89% in the ciKMC arm against 45% in the control arm (aPR: 1.62, 95% CI: 1.45−1.81). Our study findings suggest that promotion of ciKMC can improve effective breastfeeding, EBF and maternal satisfaction related to breastfeeding in LBW infants.publishedVersionPeer reviewe

Effect of Community-Initiated Kangaroo Mother Care on Fecal Biomarkers of Gut Function in Low Birth Weight Infants in North India : A Randomized Clinical Trial

This individually randomized trial was conducted to estimate the effect of promoting community-initiated Kangaroo Mother Care (ciKMC) in low birth weight (LBW) infants on gut inflammation and permeability. Participants included 200 stable LBW infants (weighing 1,500–2,250 g) in North India enrolled between May and October 2017. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding through home visits. The mothers in the intervention arm were supported to practice ciKMC until 28 days after birth, i.e., the neonatal period, or till the baby wriggled out of KMC position, if earlier. Infant stool specimens were collected during the first week of birth, and within 1 week after end of the neonatal period. Concentrations of fecal neopterin (nmol/L), myeloperoxidase (ng/mL), and alpha-1-antitrypsin (μg/mL) were determined using ELISA, and composite enteric enteropathy (EE) score at the end of the neonatal period was calculated by principal component analysis. We did not find any substantial difference in means between the ciKMC and control arm infants in the log-transformed values of neopterin (0.03; 95% CI −0.15 to 0.21), myeloperoxidase (0.28; 95% CI −0.05 to 0.61) and alpha-1-antitrypsin (0.02; 95% CI −0.30 to 0.34). The mean (SD) composite EE score was 13.6 (7.5) in the ciKMC and 12.4 (8.3) in the control arm infants, and the adjusted difference in means was, 0.4 (95% CI −1.8 to 2.7). Our findings suggest that the promotion of ciKMC did not affect gut inflammation and permeability in our target population of LBW infants in North India.acceptedVersionPeer reviewe

Enteral Zinc Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES Evidence on the effect of zinc supplementation on health outcomes in preterm or low birth weight (LBW) infants is unclear. We estimated the effect of enteral zinc versus no zinc supplementation in human milk fed preterm or LBW infants on mortality, growth, morbidities, and neurodevelopment. METHODS Data sources include PubMed, Cochrane Central and Embase databases through March 24, 2021. Study selection was randomized or quazi-experimental trials. Two reviewers independently screened, extracted data, and assessed quality. We reported pooled relative risks (RR) for categorical outcomes, and mean differences (MD) for continuous outcomes. RESULTS Fourteen trials with 9940 preterm or LBW infants were included. Moderate to low certainty evidence showed that enteral zinc supplementation had little or no effect on mortality (risk ratio 0.73, 95% confidence interval [CI] 0.46 to 1.16), but increased weight (MD 378.57, 95% CI 275.26 to 481.88), length (MD 2.92, 95% CI 1.53 to 4.31), head growth (MD 0.56, 95% CI 0.23 to 0.90), and decreased diarrhea (RR 0.81; 95% CI 0.68 to 0.97). There was no effect on acute respiratory infections, bacterial sepsis, and psychomotor development scores. The effect of zinc supplementation on mental development scores is inconclusive. There was no evidence of serious adverse events. Eight trials had some concerns or high risk of bias, small-sized studies, and high heterogeneity between trials led to moderate to very low certainty of evidence. CONCLUSIONS Zinc supplementation in preterm or LBW infants have benefits on growth and diarrhea prevention. Further research is needed to generate better quality evidence.publishedVersio

Enteral Vitamin D Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES Many preterm and low birth weight (LBW) infants have low vitamin D stores. The objective of this study was to assess effects of enteral vitamin D supplementation compared with no vitamin D supplementation in human milk fed preterm or LBW infants. METHODS Data sources include Cochrane Central Register of Controlled Trials, Medline, and Embase from inception to March 16, 2021. The study selection included randomized trials. Data were extracted and pooled with fixed and random-effects models. RESULTS We found 3 trials (2479 participants) that compared vitamin D to no vitamin D. At 6 months, there was increase in weight-for-age z-scores (mean difference 0.12, 95% confidence interval [CI] 0.01 to 0.22, 1 trial, 1273 participants), height-for-age z-scores (mean difference 0.12, 95% CI 0.02 to 0.21, 1 trial, 1258 participants); at 3 months there was decrease in vitamin D deficiency (risk ratio 0.58, 95% CI 0.49 to 0.68, I2=58%, 2 trials, 504 participants) in vitamin D supplementation groups. However, there was little or no effect on mortality, any serious morbidity, hospitalization, head circumference, growth to 6 years and neurodevelopment. The certainty of evidence ranged from very low to moderate. Fourteen trials (1969 participants) assessed dose and reported no effect on mortality, morbidity, growth, or neurodevelopment, except on parathyroid hormone and vitamin D status. No studies assessed timing. Limitations include heterogeneity and small sample size in included studies. CONCLUSIONS Enteral vitamin D supplementation improves growth and vitamin D status in preterm and LBW infants.publishedVersio

Enteral Iron Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES Iron is needed for growth and development of infants globally, but preterm and low birth weight (LBW) infants are at risk for severe iron deficiencies. To assess the effect of enteral iron supplementation on mortality, morbidity, growth, and neurodevelopment outcomes in preterm or LBW infants fed human milk. Secondary objectives were to assess the effect on biomarkers and dose and timing. METHODS Data sources include PubMed, Embase and Cochrane Library databases to March 16, 2021. Study Selection includes controlled or quasi experimental study designs. Two reviewers independently extracted data. RESULTS Eight trials (eleven reports; 1093 participants, 7 countries) were included. No trials reported mortality. At latest follow-up, there was little effect on infection (very low certainty evidence, 4 studies, 401 participants, relative risk [RR] 0.98, 95% confidence interval [95% CI] 0.56 to 1.73, I2 = 0.00%) and necrotising enterocolitis (3 studies, 375 participants, RR 1.47, 95% CI 0.68 to 3.20, I2 = 0.00%). There was an increase in linear growth (length) (moderate certainty evidence, 3 studies, 384 participants, mean difference 0.69 cm, 95% CI 0.01 to 1.37, I2 = 0%) but little effect on weight, head circumference, or cognitive development. There was an improvement in anemia (moderate certainty evidence, 2 studies, 381 participants, RR 0.25, 95% CI 0.10 to 0.62, I2 = 0.00%) but no effect on serum ferritin. Limitations include heterogeneity in the included studies. CONCLUSIONS There are important benefits for human milk-fed preterm and LBW infants from enteral iron supplementation. However, more randomized control trials are required to improve the certainty of evidence.publishedVersio

Enteral Multiple Micronutrient Supplementation in Preterm and Low Birth Weight Infants: A Systematic Review and Meta-analysis

OBJECTIVES To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. RESULTS Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight-for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. CONCLUSIONS Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment.publishedVersio