Delayed Umbilical Cord Clamping Improves Iron Status at 6 Months of Age

Abstract

Source: Chaparro CM, Neufeld LM, Alavez GT, et al. Effect of timing of umbilical cord clamping on iron status in Mexican infants: a randomised controlled trial. Lancet. 2006;367:1997–2004; doi:10.1016/S0140-6736(06)68889-2.Iron deficiency is an important public health problem in developing nations.1 Researchers from the University of California, Davis, Mexico’s National Institute of Public Health, Cuernavaca, and the Hospital de Gineco Obstetricia 4 “Luis Castelazo Ayala,” Mexico City, studied the effect of delayed umbilical cord clamping on infants’ hematological and iron status at 6 months of age. Women in labor with term, uncomplicated pregnancies expected to vaginally deliver healthy infants were enrolled and randomly assigned to early (within 10 seconds) or delayed (2 minutes) umbilical cord clamping. Venous blood was collected from the mother before delivery and from the placenta after delivery to assess maternal and fetal iron status. Capillary blood was collected from infants at 4–8 hours of age to assess hematological parameters, and morbidity data were collected at 3 and 14 days of life. Dietary and growth data were obtained at 2, 4, and 6 months of age, and venous blood was collected at 6 months. The primary outcome measure was presence of anemia (hemoglobin <11.7 g/dL [equivalent to 10.5 g/dL adjusted for altitude]) and iron deficiency (ferritin level <9 mcg/L) in infants at 6 months of age.A total of 476 mothers were randomized, and 328 infants (69%) completed the study and had blood testing at 6 months. Despite random group assignment, mothers assigned to delayed clamping had higher hemoglobin, mean corpuscular volume (MCV), and ferritin values prior to delivery than mothers assigned to early clamping, but placental blood ferritin values were not significantly different between groups. At 4–8 hours of age, hemoglobin and hematocrit values were significantly higher among infants in the delayed clamping group than in the early group (hematocrit difference 2.5% [95% CI, 0.8%–4.1%]), but only 2 infants had hematocrit values greater than 65% (66% and 68%) confirmed by venous specimen. There was no significant difference in the rate of reported neonatal jaundice. At 6 months of age, there was no difference between groups in hemoglobin or hematocrit values, or in the prevalence of anemia. However, infants in the delayed clamping group had significantly lower rates of iron deficiency (2% vs 8%) and iron deficiency anemia (0% vs 4%), defined as anemia combined with iron deficiency; significantly higher MCV, mean corpuscular hemoglobin, and ferritin values; and higher estimated body iron stores (47 vs 44 mg/kg) when compared to infants in the early clamping group. Delayed cord clamping had significantly greater effects on body iron stores among infants born to mothers with low prenatal ferritin levels, infants with lower birthweight (2500–3000g), and infants who did not receive iron-fortified formula in the first 6 months.Dr. Aldous has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of a commercial product/device. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Iron deficiency has a significant effect on cognitive development in young children.2 Efforts to decrease the prevalence of iron deficiency in developing nations continue to face major challenges.1 This study suggests that simply delaying clamping of the umbilical cord for 2 minutes after birth can increase body iron stores in newborns, with measurable effects lasting at least 6 months. The study is well done, although the loss to follow-up was higher than ideal. Mothers assigned to delayed clamping happened to have greater prenatal iron stores than those assigned to early clamping and it is possible that this difference was responsible for the improved iron status of their infants. However, adjustment for maternal prenatal ferritin level did not change the results, and the effect is consistent with previous studies of shorter term outcomes cited by the authors. In the present study, delayed cord clamping was not associated with complications, although a larger study would be required to better evaluate the risk of rare adverse effects. For example, by increasing neonatal hemoglobin concentration, delayed clamping might also be expected to increase the risk of hyperviscosity. Only 2 infants in the delayed clamping group had hematocrits above 65% and neither suffered any symptoms or complications as a result. Given that no hyperviscosity resulting in clinical symptoms or complications was observed among the 187 infants in the delayed clamping group, the true rate of hyperviscosity (or any other complication not observed) can be assumed to be between 0% and 1.6% (3/187).3 Such potential risks must be weighed against the apparent benefit of protection from iron deficiency and iron deficiency anemia in a period of tremendous developmental importance.