Two-Year Outcomes of Umbilical Cord Milking in Nonvigorous Infants: A Secondary Analysis of the MINVI Randomized Clinical Trial.

Importance: Compared with early cord clamping (ECC), umbilical cord milking (UCM) reduces delivery room cardiorespiratory support, hypoxic-ischemic encephalopathy, and therapeutic hypothermia in nonvigorous near-term and full-term infants. However, UCM postdischarge outcomes are not known. Objective: To determine the 2-year outcomes of children randomized to UCM or ECC at birth in the Milking in Nonvigorous Infants (MINVI) trial. Design, Setting, and Participants: A secondary analysis to evaluate longer-term outcomes of a cluster-randomized crossover trial was conducted from January 9, 2021, to September 25, 2023. The primary trial took place in 10 medical centers in the US, Canada, and Poland from January 5, 2019, to June 1, 2021, and hypothesized that UCM would reduce admission to the neonatal intensive care unit compared with ECC; follow-up concluded September 26, 2023. The population included near-term and full-term infants aged 35 to 42 weeks' gestation at birth who were nonvigorous; families provided consent to complete developmental screening questionnaires through age 2 years. Intervention: UCM and ECC. Main Outcomes and Measures: Ages and Stages Questionnaire, 3rd Edition (ASQ-3) and Modified Checklist for Autism in Toddlers, Revised/Follow-Up (M-CHAT-R/F) questionnaires at ages 22 to 26 months. Intention-to-treat analysis and per-protocol analyses were used. Results: Among 1730 newborns from the primary trial, long-term outcomes were evaluated in 971 children (81%) who had ASQ-3 scores available at 2 years or died before age 2 years and 927 children (77%) who had M-CHAT-R/F scores or died before age 2 years. Maternal and neonatal characteristics by treatment group were similar, with median birth gestational age of 39 (IQR, 38-40) weeks in both groups; 224 infants (45%) in the UCM group and 201 (43%) in the ECC group were female. The median ASQ-3 total scores were similar (UCM: 255 [IQR, 225-280] vs ECC: 255 [IQR, 230-280]; P = .87), with no significant differences in the ASQ-3 subdomains. Medium- to high-risk M-CHAT-R/F scores were also similar (UCM, 9% [45 of 486] vs ECC, 8% [37 of 441]; P = .86). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial among late near-term and full-term infants who were nonvigorous at birth, ASQ-3 scores at age 2 years were not significantly different between the UCM and ECC groups. Combined with previously reported important short-term benefits, this follow-up study suggests UCM is a feasible, no-cost intervention without longer-term neurodevelopmental risks of cord milking in nonvigorous near-term and term newborns. Trial Registration: ClinicalTrials.gov Identifier: NCT03631940.

Impact of early versus delayed umbilical cord clamping on term neonates' haemoglobin levels: a randomized controlled trial.

OBJECTIVE: To compare the effects of early and delayed cord clamping on the haemoglobin levels of neonates delivered at term. METHODS: This randomized controlled trial enrolled pregnant women during the second stage of labour. They were randomized into either the early cord clamping (ECC) group or the delayed cord clamping (DCC) group in the ratio of 1:1. Following delivery of the baby, the umbilical cords of participants in the ECC group were clamped within 30 s of delivery of the neonate while those of participants in the DCC group were clamped after 2 min from the delivery of the neonate. The primary outcome measure was the effect of ECC and DCC on the haemoglobin levels of neonates delivered at term. RESULTS: A total of 270 pregnant women were enrolled in the study. Their baseline sociodemographic and clinical characteristics were similar in both groups. There was no significant difference in the mean haemoglobin level between ECC and DCC groups at birth. The mean haemoglobin level of the neonates at 48 h postpartum was significantly higher in the DCC group than the ECC group. CONCLUSION: DCC at birth was associated with a significant increase in neonatal haemoglobin levels at 48 h postpartum when compared with ECC.Trial Registration: The trial was registered at Pan African Clinical Trial Registry with approval number PACTR202206735622089.

Ventilatory Assistance Before Umbilical Cord Clamping in Extremely Preterm Infants: A Randomized Clinical Trial.

Importance: Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. Objective: To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death. Design, Setting, and Participants: This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth. Intervention: After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation. Main Outcomes and Measures: The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs. Results: Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort. Conclusions and Relevance: This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight. Trial Registration: ClinicalTrials.gov Identifier: NCT02742454.

A randomised controlled trial comparing umbilical cord milking to delayed cord clamping at birth in preterm infants 28-36 weeks gestational age.

Delayed cord clamping (DCC) is an established practice in perinatology with multiple benefits. However, in instances where the implementation of DCC is not viable, it needs alternatives, especially during caesarean deliveries. A non-inferiority randomized, non-blinded, trial was conducted at a tertiary care referral unit in South India among the preterm newborns (28-36 weeks) randomized to DCC as opposed to intact-umbilical cord milking (UCM). The primary objective was to compare the mean haemoglobin values between the two groups, and the secondary outcome was to compare death and/or major IVH (> Grade II). Of the 132 eligible newborn infants, 99 were randomized to two study groups. Of the 59 and 40 randomised to UCM and DCC, 54 and 36 received the allocated intervention respectively. Preterm infants who underwent UCM had significantly higher haemoglobin (19.97 ± 1.44) as compared to DCC group (18.62 ± 0.98) p-0.0001. The rates of mortality and/or major IVH were comparable between the two groups. CONCLUSION: UCM may be a feasible alternative to DCC especially in settings where the latter is not achievable, without increasing the risk of adverse effects to the preterm infants, this finding needing further confirmation with larger sample. TRIAL REGISTRATION: CTRI (Clinical Trial Registry-India) registration number: CTRI/2020/04/024566 (registered prospectively on 13/04/2020). WHAT IS KNOWN: • Delayed cord clamping (DCC) is recommended as a standard of care for all the stable term and preterm newborn babies at birth. WHAT IS NEW: • Intact umbilical cord milking may be a reasonable choice of cord management when DCC is unsuccessful, without increasing adverse effects for the new born.

Does delayed cord clamping result in higher maternal blood loss in primary cesarean sections? A retrospective comparative study.

OBJECTIVES: The University Hospital Basel implemented delayed umbilical cord clamping of 30-60 s in all laboring women on April 1, 2020. This practice has been widely researched showing substantial benefit for the neonate. Few studies focused on maternal blood loss. The objective of our retrospective comparative study was to assess the impact of immediate vs. delayed cord clamping on maternal blood loss in primary scheduled cesarean sections. METHODS: We analyzed data of 98 women with singleton gestations undergoing primary scheduled cesarean section at term. Data from procedures with early cord clamping (ECC) were compared to those after implementation of delayed cord clamping (DCC). Primary outcomes were perioperative change in maternal hemoglobin levels, estimated and calculated blood loss. Secondary outcomes included duration of cesarean section and neonatal data. RESULTS: There was a statistically significant difference in the mean perioperative decline of hemoglobin of 10.4 g/L (SD=7.92) and 18.7 g/L (SD=10.4) between the ECC and DCC group, respectively (p<0.001). The estimated (482 mL in ECC vs. 566 mL in DCC (p=0.011)) and the calculated blood loss (438 mL in ECC vs. 715 mL in DCC (p=0.002)) also differed significantly. Secondary outcomes showed no significant differences. CONCLUSIONS: In our study DCC resulted in a statistically significant higher maternal blood loss. In our opinion the widely researched neonatal benefit of DCC outweighs the risk of higher maternal blood loss in low-risk patients. However, maternal risks must be minimized, improvements to preoperative blood management and operative techniques are required.

Deferred cord clamping to improve neonatal blood values: A systematic review and meta-analysis.

BACKGROUND: Practices related to umbilical cord clamping at birth should be evidence-based. Deferred cord clamping, compared to immediate cord clamping, shows benefits for preterm neonates but this may also apply to healthy term neonates. Different blood sampling techniques are used to measure effect of deferred and immediate cord clamping. OBJECTIVE: To assess the statistical and effect size differences between blood biomarkers from umbilical cord and capillary blood samples of healthy term neonates following either immediate or deferred cord clamping. DESIGN: Systematic review and meta-analysis. METHODS: The databases PubMed, Medline, CENTRAL, CINAHL and EMBASE were systematically searched. We included studies with a randomised clinical trial design comparing deferred and immediate cord clamping among healthy term neonates born by a spontaneous vaginal birth, reporting on blood biomarkers. Studies including caesarean births and premature births/neonates were excluded. Study attributes, sampling technique, blood biomarkers, mean differences, and standard deviations were extracted. The standardised mean differences (SMD) and sampling errors were calculated for effect size estimation. Meta-analyses were performed if ≥2 studies reported the same outcome using RevMan 5. Subgroup analyses distinguished effects from umbilical cord and capillary blood samples. Moderator tests and publication bias analyses were performed using JASP. RESULTS: Fifteen studies were included for analysis. The biomarkers haematocrit, haemoglobin, and bilirubin were reported in ≥2 studies and thus eligible for pooling. No differences were found in haemoglobin (SMD -0.04, 95%CI -0.57 to 0.49) or bilirubin values (SMD 0.13, 95%CI -0.03 to 0.28) between umbilical cord blood samples collected after deferred or immediate cord clamping. Deferred cord clamping led to lower haematocrit values (SMD -0.3, 95%CI -0.53 to -0.07). Higher haematocrit (SMD 0.67, 95%CI 0.37 to 0.97) and haemoglobin values (SMD 0.76, 95%CI 0.56 to 0.97) from capillary blood samples, collected 2 to 72 h postpartum, showed when cord clamping was deferred. No effect was found on bilirubin values (SMD 0.13, 95%CI -0.03 to 0.28) irrespective of the sampling technique. CONCLUSIONS: Blood collected after deferred umbilical cord clamping showed increased haemoglobin and haematocrit values up to 72 h after birth, opposed to bilirubin values. Clinical evaluation of blood biomarkers from the umbilical cord shows different values compared to capillary blood. Sampling time and technique therefore seem essential in estimating the effects of deferred cord clamping. TWEETABLE ABSTRACT: This meta-analysis shows that sampling time and technique are essential in estimating the effects of deferred cord clamping on neonatal blood values.

Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

Maternal bleeding complications and neonatal outcomes following early versus delayed umbilical cord clamping in cesarean deliveries for very low birthweight infants.

OBJECTIVE: Determine effect of at least 60 s delayed cord clamping (DCC) on postpartum hemorrhage and maternal estimated blood loss (EBL) in very low birth weight (VLBW) cesarean deliveries when compared to early cord clamping (ECC). STUDY DESIGN: Retrospective study of VLBW infants at birth. Maternal pre- and post-operative hemoglobin, EBL, and neonatal outcomes were collected. RESULTS: In total, 620 VLBW infants (DCC = 166, ECC = 454) born to 545 mothers (DCC = 155, ECC = 390) were included. Maternal PPH between DCC was 8% versus ECC was 10% p = 0.52. There were no differences in estimated blood loss or rate of maternal blood transfusion between groups. The post-operative hemoglobin was lower in infants receiving ECC compared to DCC (10.4 [9.4-11.5] versus 10.8 [10.1-11.9] g/dl, p = 0.01). In comparing pre-operative to post-operative hemoglobin there was no difference between DCC and ECC (-1.2 [-2.0 to -0.3] versus -1.2 [-2.1 to -0.6] g/dl, p = 0.46). CONCLUSION: DCC of at least 60 s did not increase maternal bleeding complications during VLBW cesarean delivery. To our knowledge, this retrospective study is the largest sample size to date of preterm cesarean deliveries to support maternal safety regarding bleeding complications after delayed cord clamping.

Effect of breathing on venous return during delayed cord clamping: an observational study.

OBJECTIVE: To investigate the effect of spontaneous breathing on venous return in term infants during delayed cord clamping at birth. METHODS: Echocardiographic ultrasound recordings were obtained directly after birth in healthy term-born infants. A subcostal view was used to obtain an optimal view of the inferior vena cava (IVC) entering the right atrium, including both the ductus venosus (DV) and the hepatic vein (HV). Colour Doppler was used to assess flow direction and flow velocity. Recordings continued until the umbilical cord was clamped and were stored in digital format for offline analyses. RESULTS: Ultrasound recordings were obtained in 15 infants, with a median (IQR) gestational age of 39.6 (39.0-40.9) weeks and a birth weight of 3560 (3195-4205) g. Flow was observed to be antegrade in the DV and HV in 98% and 82% of inspirations, respectively, with flow velocity increasing in 74% of inspirations. Retrograde flow in the DV was observed sporadically and only occurred during expiration. Collapse of the IVC occurred during 58% of inspirations and all occurred caudal to the DV inlet (100%). CONCLUSION: Spontaneous breathing was associated with collapse of the IVC and increased antegrade DV and HV flow velocity during inspiration. Therefore, inspiration appears to preferentially direct blood flow from the DV into the right atrium. This indicates that inspiration could be a factor driving placental transfusion in infants.

Effects of delayed versus immediate umbilical cord clamping in reducing death or major disability at 2 years corrected age among very preterm infants (APTS): a multicentre, randomised clinical trial.

BACKGROUND: Very preterm infants are at increased risk of adverse outcomes in early childhood. We assessed whether delayed clamping of the umbilical cord reduces mortality or major disability at 2 years in the APTS Childhood Follow Up Study. METHODS: In this long-term follow-up analysis of the multicentre, randomised APTS trial in 25 centres in seven countries, infants (<30 weeks gestation) were randomly assigned before birth (1:1) to have clinicians aim to delay clamping for 60 s or more or clamp within 10 s of birth, both without cord milking. The primary outcome was death or major disability (cerebral palsy, severe visual loss, deafness requiring a hearing aid or cochlear implants, major language or speech problems, or cognitive delay) at 2 years corrected age, analysed in the intention-to-treat population. This trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12610000633088). FINDINGS: Between Oct 21, 2009, and Jan 6, 2017, consent was obtained for follow-up for 1531 infants, of whom 767 were randomly assigned to delayed clamping and 764 to immediate clamping. 384 (25%) of 1531 infants were multiple births, 862 (56%) infants were male, and 505 (33%) were born before 27 weeks gestation. 564 (74%) of 767 infants assigned to delayed clamping and 726 (96%) of 764 infants assigned to immediate clamping received treatment that fully adhered to the protocol. Death or major disability was determined in 1419 (93%) infants and occurred in 204 (29%) of 709 infants who were assigned to delayed clamping versus 240 (34%) of 710 assigned to immediate clamping, (relative risk [RR]) 0·83, 95% CI 0·72-0·95; p=0·010). 60 (8%) of 725 infants in the delayed clamping group and 81 (11%) of 720 infants in the immediate clamping group died by 2 years of age (RR 0·70, 95% CI 0·52-0·95); among those who survived, major disability at 2 years occurred in 23% (144/627) versus 26% (159/603) of infants, respectively (RR 0·88, 0·74-1·04). INTERPRETATION: Clamping the umbilical cord at least 60 s after birth reduced the risk of death or major disability at 2 years by 17%, reflecting a 30% reduction in relative mortality with no difference in major disability. FUNDING: Australian National Health and Medical Research Council.

Association of Umbilical Cord Management Strategies With Outcomes of Preterm Infants: A Systematic Review and Network Meta-analysis.

Importance: It is unclear which umbilical cord management strategy is the best for preventing mortality and morbidities in preterm infants. Objective: To systematically review and conduct a network meta-analysis comparing 4 umbilical cord management strategies for preterm infants: immediate umbilical cord clamping (ICC), delayed umbilical cord clamping (DCC), umbilical cord milking (UCM), and UCM and DCC. Data Sources: PubMed, Embase, CINAHL, and Cochrane CENTRAL databases were searched from inception until September 11, 2020. Study Selection: Randomized clinical trials comparing different umbilical cord management strategies for preterm infants were included. Data Extraction and Synthesis: Data were extracted for bayesian random-effects meta-analysis to estimate the relative treatment effects (odds ratios [OR] and 95% credible intervals [CrI]) and surface under the cumulative ranking curve values. Main Outcomes and Measures: The primary outcome was predischarge mortality. The secondary outcomes were intraventricular hemorrhage, severe intraventricular hemorrhage, need for packed red blood cell transfusion, and other neonatal morbidities. Confidence in network meta-analysis software was used to assess the quality of evidence and grade outcomes. Results: Fifty-six studies enrolled 6852 preterm infants. Compared with ICC, DCC was associated with lower odds of mortality (22 trials, 3083 participants; 7.6% vs 5.0%; OR, 0.64; 95% CrI, 0.39-0.99), intraventricular hemorrhage (25 trials, 3316 participants; 17.8% vs 15.4%; OR, 0.73; 95% CrI, 0.54-0.97), and need for packed red blood cell transfusion (18 trials, 2904 participants; 46.9% vs 38.3%; OR, 0.48; 95% CrI, 0.32-0.66). Compared with ICC, UCM was associated with lower odds of intraventricular hemorrhage (10 trials, 645 participants; 22.5% vs 16.2%; OR, 0.58; 95% CrI, 0.38-0.84) and need for packed red blood cell transfusion (9 trials, 688 participants; 47.3% vs 32.3%; OR, 0.36; 95% CrI, 0.23-0.53), with no significant differences for other secondary outcomes. There was no significant difference between UCM and DCC for any outcome. Conclusions and Relevance: Compared with ICC, DCC was associated with the lower odds of mortality in preterm infants. Compared with ICC, DCC and UCM were associated with reductions in intraventricular hemorrhage and need for packed red cell transfusion. There was no significant difference between UCM and DCC for any outcome. Further studies directly comparing DCC and UCM are needed.

Hepcidin is a relevant iron status indicator in infancy: results from a randomized trial of early vs. delayed cord clamping.

BACKGROUND: We aimed to evaluate whether serum hepcidin is a useful indicator of iron status in infants. METHODS: Term infants (n = 400) were randomized to delayed (≥180 s) or early (≤10 s) cord clamping (CC). Iron status was assessed at 4 and 12 months. In all cases with iron depletion or iron deficiency (ID) (as defined in "Methods") (n = 30) and 97 randomly selected iron-replete infants, we analyzed hepcidin and explored its correlation to the intervention, iron status, and perinatal factors. RESULTS: Serum hepcidin concentrations were significantly lower in the early CC group at both time points and in ID infants at 4 months. Median (2.5th-97.5th percentile) hepcidin in non-ID infants in the delayed CC group (suggested reference) was 64.5 (10.9-142.1), 39.5 (3.5-157.7), and 32.9 (11.2-124.2) ng/mL in the cord blood and at 4 and 12 months, respectively. The value of 16 ng/mL was a threshold detecting all cases of iron depletion/ID at 4 months. No similar threshold for ID was observed at 12 months. The strongest predictor of hepcidin at both ages was ferritin. CONCLUSIONS: Hepcidin is relevant as iron status indicator in early infancy and may be useful to detect ID. Levels <16 ng/mL at 4 months of age indicates ID. IMPACT: Serum hepcidin is a relevant indicator of iron status in early infancy. Normal reference in healthy infants is suggested in this study. Serum hepcidin may be useful in clinical practice to detect iron deficiency.