Transmission of cytomegalovirus via breast milk in low birth weight and premature infants: a systematic review and meta-analysis
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ABSTRACT: Background
This study aimed to investigate the transmission of cytomegalovirus (CMV) via breast milk in low birth weight (LBW) and premature infants and its effects. Methods
PubMed, Medline, Cochrane Library, and Embase were searched for studies (without language and time restriction) published before March 27, 2020, that examined the effect of CMV transmitted by breast milk on LBW and premature infants. The rates of breast milk-acquired CMV infection, CMV-related symptoms, and CMV-related sepsis-like syndrome (CMV-SLS) in LBW and premature infants were pooled from each study. Results
Eighteen studies with 1920 LBW and premature infants were included. The pooled CMV infection rate from breast milk for infants fed untreated breast milk was significantly higher than those fed frozen breast milk [19.3, 95% confidence interval (CI) = 11.8–29.9% vs. 13.5, 95% CI = 8.0–22.0%, P < 0.01). Similarly, the pooled CMV infection rate for infants fed untreated breast milk was significantly higher than those with mixed feeding (P < 0.0001). The mixed feeding group had a significantly lower rate of CMV-related symptoms than the other groups (2.4%, P < 0.01). Conclusions
These findings suggested a higher CMV infection rate in LBW or premature infants fed untreated breast milk than other feeding groups. Studies on the long-term outcomes of CMV infection transmitted from breast milk are needed to address the optimal feeding practice. Supplementary Information
The online version contains supplementary material available at 10.1186/s12887-021-02984-7.
SUBMITTER: Hu X
PROVIDER: S-EPMC8607598 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportancePostnatal cytomegalovirus (CMV) infection can cause serious morbidity and mortality in very low-birth-weight (VLBW) infants. The primary sources of postnatal CMV infection in this population are breast milk and blood transfusion. The current risks attributable to these vectors, as well as the efficacy of approaches to prevent CMV transmission, are poorly characterized.ObjectiveTo estimate the risk of postnatal CMV transmission from 2 sources: (1) transfusion of CMV-seronegative and leukoreduced blood and (2) maternal breast milk.Design, setting, and participantsA prospective, multicenter birth-cohort study was conducted from January 2010 to June 2013 at 3 neonatal intensive care units (2 academically affiliated and 1 private) in Atlanta, Georgia. Cytomegalovirus serologic testing of enrolled mothers was performed to determine their status. Cytomegalovirus nucleic acid testing (NAT) of transfused blood components and breast milk was performed to identify sources of CMV transmission. A total of 539 VLBW infants (birth weight, ≤ 1500 g) who had not received a blood transfusion were enrolled, with their mothers (n = 462), within 5 days of birth. The infants underwent serum and urine CMV NAT at birth to evaluate congenital infection and surveillance CMV NAT at 5 additional intervals between birth and 90 days, discharge, or death.ExposuresBlood transfusion and breast milk feeding.Main outcomes and measuresCumulative incidence of postnatal CMV infection, detected by serum or urine NAT.ResultsThe seroprevalence of CMV among the 462 enrolled mothers was 76.2% (n = 352). Among the 539 VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks was 6.9% (95% CI, 4.2%-9.2%); 5 of 29 infants (17.2%) with postnatal CMV infection developed symptomatic disease or died. A total of 2061 transfusions were administered among 57.5% (n = 310) of the infants; none of the CMV infections was linked to transfusion, resulting in a CMV infection incidence of 0.0% (95% CI, 0.0%-0.3%) per unit of CMV-seronegative and leukoreduced blood. Twenty-seven of 28 postnatal infections occurred among infants fed CMV-positive breast milk (12-week incidence, 15.3%; 95% CI, 9.3%-20.2%).Conclusions and relevanceTransfusion of CMV-seronegative and leukoreduced blood products effectively prevents transmission of CMV to VLBW infants. Among infants whose care is managed with this transfusion approach, maternal breast milk is the primary source of postnatal CMV infection.Trial registrationclinicaltrials.gov Identifier: NCT00907686.
| S-EPMC4392178 | biostudies-literature
Project description:AimBreast milk feeding is linked to improved neurodevelopmental outcomes in very low birth weight (VLBW) infants, though the mechanisms are not well understood. This study utilised quantitative magnetic resonance imaging (qMRI) techniques to compare brain growth and white matter development in preterm infants receiving primarily breast milk versus formula feeds.MethodsWe prospectively enrolled infants born at very low birth weight (<1500 g) and <32 weeks gestational age and performed MRI at term-equivalent age. We utilised volumetric segmentation to calculate regional and total brain volumes and diffusion tensor imaging to evaluate white matter microstructural organisation. Daily nutritional data were extracted from the medical record.ResultsNutritional and MRI data were obtained for 68 infants admitted within the first week of life (44 breast milk and 24 formula). Breast milk-fed infants demonstrated significantly larger total brain volumes (P = .04) as well as volumes in the amygdala-hippocampus and cerebellum (P < .01) compared with formula-fed. Infants receiving breast milk also demonstrated greater white matter microstructural organisation in the corpus callosum, posterior limb of internal capsule and cerebellum (P < .01 to .03).ConclusionVLBW infants receiving primarily breast milk versus preterm formula in this small exploratory study demonstrated significantly greater regional brain volumes and white matter microstructural organisation by term-equivalent age.
| S-EPMC7347461 | biostudies-literature
Project description:There has been a dramatic rise in preterm births in developed countries owing to changes in clinical practices and greater use of assisted reproductive techniques. However, few studies have examined the growth and outcomes of preterm infants according to the type of feeding (with fortified breast milk or formula). The purpose of this study was to examine the effect of breast milk feedings and formula on the growth and short-term outcomes of preterm infants in Hong Kong. In a single-center retrospective cohort study, we included 642 preterm infants at gestational age <37 weeks with birth weights <2200 g. According to World Health Organization criteria, 466 were classified as low birth weight (LBW) infants (?1500 g and <2200 g) and 176 were classified as very low birth weight (VLBW) infants (<1500 g). The mothers of approximately 80% of VLBW infants and 60% LBW infants initiated breast milk feeding. When compared with no breast milk intake, LBW infants that received breast milk were significantly more likely to have growth z-scores closer to the median of the reference population on admission and experienced slower weight gain from birth to discharge. When breast milk was categorized by percent of total enteral intake, significant differences were seen among LBW infants, with lower percentages of small-for-gestational-age (SGA) status at discharge with increased proportions of breast milk intake. Our results suggest that LBW infants fed breast milk had better growth z-scores and lower SGA status at discharge compared with those predominately fed preterm formula.
| S-EPMC5452250 | biostudies-other
Project description:BACKGROUND:When sufficient maternal breast milk is not available, alternative forms of enteral nutrition for preterm or low birth weight (LBW) infants are donor breast milk or artificial formula. Donor breast milk may retain some of the non-nutritive benefits of maternal breast milk for preterm or LBW infants. However, feeding with artificial formula may ensure more consistent delivery of greater amounts of nutrients. Uncertainty exists about the balance of risks and benefits of feeding formula versus donor breast milk for preterm or LBW infants. OBJECTIVES:To determine the effect of feeding with formula compared with donor breast milk on growth and development in preterm or low birth weight (LBW) infants. SEARCH METHODS:We used the Cochrane Neonatal search strategy, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5), Ovid MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (3 May 2019), as well as conference proceedings, previous reviews, and clinical trials. SELECTION CRITERIA:Randomised or quasi-randomised controlled trials (RCTs) comparing feeding with formula versus donor breast milk in preterm or LBW infants. DATA COLLECTION AND ANALYSIS:Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios (RRs) and risk differences (RDs) for dichotomous data, and mean differences (MDs) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in subgroup analyses. We assessed the certainty of evidence for the main comparison at the outcome level using GRADE methods. MAIN RESULTS:Twelve trials with a total of 1879 infants fulfilled the inclusion criteria. Four trials compared standard term formula versus donor breast milk and eight compared nutrient-enriched preterm formula versus donor breast milk. Only the five most recent trials used nutrient-fortified donor breast milk. The trials contain various weaknesses in methodological quality, specifically concerns about allocation concealment in four trials and lack of blinding in most of the trials. Most of the included trials were funded by companies that made the study formula.Formula-fed infants had higher in-hospital rates of weight gain (mean difference (MD) 2.51, 95% confidence interval (CI) 1.93 to 3.08 g/kg/day), linear growth (MD 1.21, 95% CI 0.77 to 1.65 mm/week) and head growth (MD 0.85, 95% CI 0.47 to 1.23 mm/week). These meta-analyses contained high levels of heterogeneity. We did not find evidence of an effect on long-term growth or neurodevelopment. Formula feeding increased the risk of necrotising enterocolitis (typical risk ratio (RR) 1.87, 95% CI 1.23 to 2.85; risk difference (RD) 0.03, 95% CI 0.01 to 0.05; number needed to treat for an additional harmful outcome (NNTH) 33, 95% CI 20 to 100; 9 studies, 1675 infants).The GRADE certainty of evidence was moderate for rates of weight gain, linear growth, and head growth (downgraded for high levels of heterogeneity) and was moderate for neurodevelopmental disability, all-cause mortality, and necrotising enterocolitis (downgraded for imprecision). AUTHORS' CONCLUSIONS:In preterm and LBW infants, moderate-certainty evidence indicates that feeding with formula compared with donor breast milk, either as a supplement to maternal expressed breast milk or as a sole diet, results in higher rates of weight gain, linear growth, and head growth and a higher risk of developing necrotising enterocolitis. The trial data do not show an effect on all-cause mortality, or on long-term growth or neurodevelopment.
| S-EPMC6640412 | biostudies-literature
Project description:BackgroundWhen sufficient maternal breast milk is not available, alternative forms of enteral nutrition for preterm or low birth weight (LBW) infants are donor breast milk or artificial formula. Donor breast milk may retain some of the non-nutritive benefits of maternal breast milk for preterm or LBW infants. However, feeding with artificial formula may ensure more consistent delivery of greater amounts of nutrients. Uncertainty exists about the balance of risks and benefits of feeding formula versus donor breast milk for preterm or LBW infants.ObjectivesTo determine the effect of feeding with formula compared with donor breast milk on growth and development in preterm or low birth weight (LBW) infants.Search methodsWe used the Cochrane Neonatal search strategy, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 6), Ovid MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (until 8 June 2017), as well as conference proceedings and previous reviews.Selection criteriaRandomised or quasi-randomised controlled trials (RCTs) comparing feeding with formula versus donor breast milk in preterm or LBW infants.Data collection and analysisTwo review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios (RRs) and risk differences (RDs) for dichotomous data, and mean differences (MDs) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in subgroup analyses. We assessed the quality of evidence for the main comparison at the outcome level using "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) methods.Main resultsEleven trials, in which 1809 infants participated in total, fulfilled the inclusion criteria. Four trials compared standard term formula versus donor breast milk and seven compared nutrient-enriched preterm formula versus donor breast milk. Only the four most recent trials used nutrient-fortified donor breast milk. The trials contain various weaknesses in methodological quality, specifically concerns about allocation concealment in four trials and lack of blinding in most of the trials.Formula-fed infants had higher in-hospital rates of weight gain (mean difference (MD) 2.51, 95% confidence interval (CI) 1.93 to 3.08 g/kg/day), linear growth (MD 1.21, 95% CI 0.77 to 1.65 mm/week) and head growth (MD 0.85, 95% CI 0.47 to 1.23 mm/week). We did not find evidence of an effect on long-term growth or neurodevelopment. Formula feeding increased the risk of necrotising enterocolitis (typical risk ratio (RR) 1.87, 95% CI 1.23 to 2.85; risk difference (RD) 0.03, 95% CI 0.01 to 0.06).The GRADE quality of evidence was moderate for rates of weight gain, linear growth, and head growth (downgraded for high levels of heterogeneity) and was moderate for neurodevelopmental disability, all-cause mortality, and necrotising enterocolitis (downgraded for imprecision).Authors' conclusionsIn preterm and LBW infants, feeding with formula compared with donor breast milk, either as a supplement to maternal expressed breast milk or as a sole diet, results in higher rates of weight gain, linear growth, and head growth and a higher risk of developing necrotising enterocolitis. The trial data do not show an effect on all-cause mortality, or on long-term growth or neurodevelopment.
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Project description:Very low birth weight (VLBW) and premature infants are at risk for developing postnatal cytomegalovirus (CMV) disease, including CMV-related sepsis-like syndrome (CMV-SLS) for which estimates [corrected] in the United States are lacking.We performed a systematic review and meta-analysis to estimate the pooled proportions (and 95% confidence intervals) of VLBW and premature infants born to CMV-seropositive women with breast milk-acquired CMV infection and CMV-SLS. We combined these proportions with population-based rates of CMV seropositivity, breast milk feeding, VLBW, and prematurity to estimate annual rates of breast milk-acquired CMV infection and CMV-SLS in the United States.In our meta-analysis, among 299 infants fed untreated breast milk, we estimated 19% (11%-32%) acquired CMV infection and 4% (2%-7%) developed CMV-SLS. Assuming these proportions, we estimated a rate of breast milk-acquired CMV infection among VLBW and premature infants in the United States of 6.5% (3.7%-10.9%) and 1.4% (0.7%-2.4%) of CMV-SLS, corresponding to 600 infants with CMV-SLS in 2008. Among 212 infants fed frozen breast milk, our meta-analysis proportions were 13% (7%-24%) for infection and 5% (2%-12%) for CMV-SLS, yielding slightly lower rates of breast milk-acquired CMV infection (4.4%; 2.4%-8.2%) but similar rates of CMV-SLS (1.7%; 0.7%-4.1%).Breast milk-acquired CMV infection presenting with CMV-SLS is relatively rare. Prospective studies to better define the burden of disease are needed to refine guidelines for feeding breast milk from CMV-seropositive mothers to VLBW and premature infants.
| S-EPMC4850548 | biostudies-literature
Project description:Protein content is often inadequate in donor breast milk (DBM), resulting in poor growth. The use of protein-enriched target-pooled DBM (DBM+) has not been examined. We compared three cohorts of very low birth weight (VLBW) infants, born ≤ 1500 g: DBM cohort receiving > 1-week target-pooled DBM (20 kcal/oz), MBM cohort receiving ≤ 1-week DBM, and DBM+ cohort receiving > 1-week DBM+. Infants followed a standardized feeding regimen with additional fortification per clinical discretion. Growth velocities and z-scores were calculated for the first 4 weeks (n = 69 for DBM, 71 for MBM, 70 for DBM+) and at 36 weeks post-menstrual age (n = 58, 64, 59, respectively). In total, 60.8% MBM infants received fortification >24 kcal/oz in the first 30 days vs. 78.3% DBM and 77.1% DBM+. Adjusting for SGA, length velocity was greater with DBM+ than DBM in week 1. Average weight velocity and z-score change were improved with MBM compared to DBM and DBM+, but length z-score decreased similarly across all groups. Incidences of NEC and feeding intolerance were unchanged between eras. Thus, baseline protein enrichment appears safe in stable VLBW infants. Weight gain is greatest with MBM. Linear growth comparable to MBM is achievable with DBM+, though the overall length trajectory remains suboptimal.
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Project description:BACKGROUND:Neonatal sepsis is a leading cause of child morbidity and mortality, especially in premature and low birth weight infants. Prompt antibiotic therapy is warranted, but its inappropriate use leads to bacterial resistance and adverse outcomes. Our objective is to describe the antibiotic use for late-onset sepsis in Peruvian premature infants. METHODS:This study is a prospective study as a secondary analysis of a clinical trial in 3 neonatal care units in Peru. We included infants in the first 72 hours of life, with birth weight (BW) <2000?g. We described the antibiotic use as length of therapy (LOT) per 1000 patient days (PD) and antibiotic courses. RESULTS:We included 408 neonates, with 12,204 PD of follow-up; 253 infants (62%) had a BW ?1500?g. Total antibiotic use for late-onset sepsis was 2395 LOT (196 LOT/1000 PD). Two-hundred and seventy-one patients (66.4%) did not receive antibiotics for late-onset sepsis during their hospitalization. In total, 204 antibiotic courses were administered; 92 infants (22.5%) received 1 course, and 45 (11.0%) received 2-5 antibiotic courses. Mean duration of antibiotic course was 10.8 days (standard deviation: ±7.3). We found a significant association between a lower BW and increased antibiotic use per day (P < 0.001). The most commonly used antibiotics were vancomycin (143 LOT/1000 PD), carbapenems (115 LOT/1000 PD), aminoglycosides (72 LOT/1000 PD) and ampicillin (41 LOT/1000 PD). CONCLUSIONS:Premature infants receive antibiotics for longer than recommended periods of time. Antibiotic overuse is greater in neonates with lower BW. Vancomycin is the most used antibiotic. There is an urgent need to develop antimicrobial stewardship programs in our setting.
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Project description:The heptavalent pneumococcal CRM197 conjugate vaccine (PCV-7) has been incompletely studied in very-low-birth-weight (< or =1500 g) infants.To assess PCV-7 immunogenicity in very-low-birth-weight, premature infants. We hypothesized that the frequency of postvaccine antibody concentrations > or =0.15 microg/mL would vary directly with birth weight.This was a multicenter observational study. Infants 401 to 1500 g birth weight and <32 0/7 weeks gestation, stratified by birth weight, were enrolled from 9 National Institute of Child Health and Human Development Neonatal Research Network centers. Infants received PCV-7 at 2, 4, and 6 months after birth and had blood drawn 4 to 6 weeks following the third dose. Antibodies against the 7 vaccine serotypes were measured by enzyme-linked immunosorbent assay.Of 369 enrolled infants, 244 completed their primary vaccine series by 8 months and had serum obtained. Subjects were 27.8 +/- 2.2 (mean +/- standard deviation) weeks gestation and 1008 +/- 282 g birth weight. Twenty-six percent had bronchopulmonary dysplasia and 16% had received postnatal glucocorticoids. Infants 1001 to 1500 g birth weight were more likely than those 401 to 1000 g to achieve antibody concentrations > or =0.15 microg/mL against the least 2 immunogenic serotypes (6B: 96% vs. 85%, P = 0.003 and 23F: 97% vs. 88%, P = 0.009). In multiple logistic regression analysis, lower birth weight, postnatal glucocorticoid use, lower weight at blood draw, and Caucasian race were each independently associated with antibody concentrations <0.35 microg/mL against serotypes 6B and/or 23F.When compared with larger premature infants, infants weighing < or =1000 g at birth have similar antibody responses to most, but not all, PCV-7 vaccine serotypes.
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