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Meta-Analysis
. 2010 Jan 20;2010(1):CD000229.
doi: 10.1002/14651858.CD000229.pub2.

Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage

Caroline A Crowther  1 , Danielle D Crosby, David J Henderson-Smart
Affiliations
Meta-Analysis

Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage

Caroline A Crowther et al. Cochrane Database Syst Rev. .

Abstract

Background: Preterm infants are at risk of periventricular haemorrhage. This can be a sign of brain damage that might lead to neurodevelopmental abnormalities, including cerebral palsy. It has been suggested that vitamin K might improve coagulation in preterm infants and thereby decrease the risk of periventricular haemorrhage.

Objectives: The objective of this review was to assess the effects of vitamin K administered to women at risk of imminent very preterm birth to prevent periventricular haemorrhage and associated neurological injury in the infant.

Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2008).

Selection criteria: Randomised or quasi-randomised trials of vitamin K administered parenterally or orally to women at risk of imminent preterm birth. The primary outcomes were neonatal mortality, neonatal neurological morbidity, as measured by the presence of periventricular haemorrhage (PVH) on ultrasound during the first week of life, and long-term neurodevelopment. Secondary outcomes included other neonatal morbidity and any maternal side effects.

Data collection and analysis: Two review authors independently assessed eligibility, trial quality and extracted data.

Main results: Seven trials were included, involving 607 women. The trials were of variable quality. Antenatal vitamin K was associated with a non-significant reduction in all grades of periventricular haemorrhage (risk ratio (RR) 0.76; 95% confidence interval (CI) 0.54 to 1.06) and a significant reduction in severe PVH (grades 3 and 4) (RR 0.58; 95% CI 0.37 to 0.91) for babies receiving prenatal vitamin K compared with control babies. When the two quasi-randomised trials were excluded, antenatal vitamin K was associated with a non-significant reduction in all grades of PVH (RR 0.87; 95% CI 0.60 to 1.26) and a non-significant reduction in severe PVH (RR 0.82; 95% CI 0.49 to 1.36).There was an unfavourable effect of vitamin K on development as measured by the Bayley Mental Development Index at two years of age, however these results are derived from one trial with many participants lost to follow up. No difference was found in the incidence of other neurodevelopmental abnormalities at paediatric follow up at 18 to 24 months or seven years of age between children born to mothers given vitamin K and children not so exposed.

Authors' conclusions: Vitamin K administered to women prior to very preterm birth has not been shown to significantly prevent periventricular haemorrhages in preterm infants or improve neurodevelopmental outcomes in childhood.

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Conflict of interest statement

None known.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 1 Perinatal mortality.
1.2
1.2. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 2 All periventricular haemorrhage (PVH).
1.3
1.3. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 3 Severe (grades 3 and 4) PVH.
1.4
1.4. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 4 Bayley Mental Developmental Index at 2 years.
1.5
1.5. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 5 Bayley Psychomotor Developmental Index at 2 years.
1.6
1.6. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 6 Cerebral palsy at 7 year follow up.
1.7
1.7. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 7 Wechsler Intelligence Scale for Children at 7 year follow up.
1.8
1.8. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 8 Wide Range Achievement Test at 7 year follow up.
1.9
1.9. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 9 Achenbach Teacher's Report Form at 7 year follow up.
1.10
1.10. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 10 Child Behavioral Check List total at 7 year follow up.
1.11
1.11. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 11 Maternal side effects (any).
1.12
1.12. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 12 Respiratory distress syndrome.
1.13
1.13. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 13 Patent ductus arteriosus.
1.14
1.14. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 14 Use of mechanical ventilation.
1.15
1.15. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 15 Pulmonary air leak.
1.16
1.16. Analysis
Comparison 1 Vitamin K versus control ‐ all studies, Outcome 16 Low Apgar score at 5 minutes.
2.1
2.1. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 1 Perinatal mortality.
2.2
2.2. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 2 All periventricular haemorrhage (PVH).
2.3
2.3. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 3 Severe (grades 3 and 4) PVH.
2.4
2.4. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 4 Bayley Mental Developmental Index at 2 years.
2.5
2.5. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 5 Bayley Psychomotor Developmental Index at 2 years.
2.6
2.6. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 6 Cerebral palsy at 7 year follow up.
2.7
2.7. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 7 Wechsler Intelligence Scale for Children at 7 year follow up.
2.8
2.8. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 8 Wide Range Achievement Test at 7 year follow up.
2.9
2.9. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 9 Achenbach Teacher's Report Form at 7 year follow up.
2.10
2.10. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 10 Child Behavioral Check List total at 7 year follow up.
2.11
2.11. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 11 Maternal side effect (any).
2.12
2.12. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 12 Respiratory distress syndrome.
2.13
2.13. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 13 Patent ductus arteriosus.
2.14
2.14. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 14 Pulmonary air leak.
2.15
2.15. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 15 Use of mechanical ventilation.
2.16
2.16. Analysis
Comparison 2 Vitamin K versus control ‐ excluding trials with inadequate concealment of allocation of treatment, Outcome 16 Low Apgar score at 5 minutes.
3.1
3.1. Analysis
Comparison 3 Vitamin K versus control ‐ excluding trials with inadequate randomisation and > 20% or unclear for exclusions, Outcome 1 Perinatal mortality.
3.2
3.2. Analysis
Comparison 3 Vitamin K versus control ‐ excluding trials with inadequate randomisation and > 20% or unclear for exclusions, Outcome 2 All periventricular haemorrhage (PVH).
3.3
3.3. Analysis
Comparison 3 Vitamin K versus control ‐ excluding trials with inadequate randomisation and > 20% or unclear for exclusions, Outcome 3 Severe (grades 3 and 4) PVH.
3.4
3.4. Analysis
Comparison 3 Vitamin K versus control ‐ excluding trials with inadequate randomisation and > 20% or unclear for exclusions, Outcome 4 Maternal side effect (any).
3.5
3.5. Analysis
Comparison 3 Vitamin K versus control ‐ excluding trials with inadequate randomisation and > 20% or unclear for exclusions, Outcome 5 Patent ductus arteriosus.
3.6
3.6. Analysis
Comparison 3 Vitamin K versus control ‐ excluding trials with inadequate randomisation and > 20% or unclear for exclusions, Outcome 6 Pulmonary air leak.
3.7
3.7. Analysis
Comparison 3 Vitamin K versus control ‐ excluding trials with inadequate randomisation and > 20% or unclear for exclusions, Outcome 7 Use of mechanical ventilation.
3.8
3.8. Analysis
Comparison 3 Vitamin K versus control ‐ excluding trials with inadequate randomisation and > 20% or unclear for exclusions, Outcome 8 Low Apgar score at 5 minutes.
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References

References to studies included in this review

Dickson 1994 {published data only}
    1. Dickson R, Stubbs T, Lazarchick J. Antenatal vitamin K therapy of the low‐birth‐weight infant. American Journal of Obstetrics and Gynecology 1994;170:85‐9. - PubMed
Kazzi 1989 {published data only}
    1. Kazzi N, Ilagan N, Liang K, Kazzi G, Grietsell L, Brans Y. Placental transfer of vitamin K1 in preterm pregnancy. Obstetrics and Gynecology 1990;75:334‐7. - PubMed
    1. Kazzi N, Ilagan N, Liang K, Kazzi G, Poland R. Effects of antenatal vitamin K on cord blood coagulation profile of preterm infants. Pediatric Research 1988;23:412A, Abstract no: 1267.
    1. Kazzi N, Ilagan N, Liang K, Kazzi G, Poland R. Effects of antenatal vitamin K on the incidence of IVH and mortality in preterm infants. Pediatric Research 1988;23:412A, Abstract no: 1266.
    1. Kazzi N, Ilagan N, Liang K, Kazzi G, Poland R, Grietsell L, et al. Maternal administration of vitamin K does not improve the coagulation profile of preterm infants. Pediatrics 1989;84:1045‐50. - PubMed
    1. Kazzi NJ, Ilagan NB, Liang KC, Kazzi GM, Poland RL. Does vitamin K cross the placenta in pregnancy before term? [abstract]. Pediatric Research 1988;23:412A.
Liu 2006 {published data only}
    1. Liu J, Wang Q, Gao F, He JW, Zhao JH. Maternal antenatal administration of vitamin K1 results in increasing the activities of vitamin K‐dependent coagulation factors in umbilical blood and in decreasing the incidence rate of periventricular‐intraventricular hemorrhage in premature infants. Journal of Perinatal Medicine 2006;34(2):173‐6. - PubMed
    1. Liu J, Wang Q, Zhao JH, Chen YH, Qin GL. The combined antenatal corticosteroids and vitamin K therapy for preventing periventricular‐intraventricular hemorrhage in premature newborns less than 35 weeks gestation. Journal of Tropical Pediatrics 2006;52(5):355‐9. - PubMed
Morales 1988 {published data only}
    1. Morales W, Angel J, O'Brien W, Knuppel R, Marsalisi F. The use of antenatal vitamin K in the prevention of early neonatal intraventricular hemorrhage. American Journal of Obstetrics and Gynecology 1988;159:774‐9. - PubMed
Pathak 1990 {published data only}
    1. Pathak A, Hamm CR, Eyal FG, Walter K, Rijhsinghani A, Bohlman M. Maternal vitamin K administration for prevention of intraventricular hemorrhage in preterm infants [abstract]. Pediatric Research 1990;27:219A.
Pomerance 1987 {published data only}
    1. Pomerance J, Teal J, Gogolok J, Brown S, Stewart M. Maternally administered antenatal vitamin K effect on neonatal prothrombin activity, partial thromboplastin time, and intraventricular hemorrhage. Obstetrics & Gynecology 1987;70:235‐41. - PubMed
Thorp 1994 {published data only}
    1. Lia JE, Billman D. Antepartum vitamin K and phenobarbital for preventing intraventricular hemorrhage in the premature newborn; a randomized, double‐blind, placebo‐controlled trial [letter]. Obstetrics & Gynecology 1994;83(6):1067‐8. - PubMed
    1. Thorp J, O'Connor M, Jones A, Hoffman E, Belden B. Does perinatal phenobarbital exposure affect developmental outcome at age 2?. American Journal of Perinatology 1999;16:51‐60. - PubMed
    1. Thorp J, Parriot J, Ferrette‐Smith D, Meyer B, Cohen GR, Johnson J. Antepartum vitamin K and phenobarbital for preventing intraventricular hemorrhage in the premature newborn; a randomized, double‐blind, placebo‐controlled trial. Obstetrics & Gynecology 1994;83(1):70‐6. - PubMed
    1. Thorp J, Yeast J, Cohen G, Poskin M, Peng V, Hoffman E. Does in‐utero phenobarbital lower IQ? Follow up of the intracranial hemorrhage prevention trial. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S117.
    1. Thorp JA. Antepartum vitamin K and phenobarbital for preventing intraventricular hemorrhage in the premature newborn; a randomized, double‐blind, placebo‐controlled trial [In reply]. Obstetrics and Gynecology 1994;83(6):1068‐9. - PubMed
Yang 1989 {published data only}
    1. Yang Y, Simon N, Maertens P, Brigham S, Liu P. Maternal‐fetal transport of vitamin K and its effects on coagulation in premature infants. Journal of Pediatrics 1989;115:1009‐13. - PubMed

References to studies excluded from this review

Anai 1993 {published data only}
    1. Anai T, Hirota Y, Yoshimatsu J, Oga M, Miyakawa I. Can prenatal vitamin K (phylloquinone) supplementation replace prophylaxis at birth?. Obstetrics & Gynecology 1993;81:251‐4. - PubMed

References to studies awaiting assessment

Liu 2005 {published data only}
    1. Liu J, Wang Q, Chen YH, Qin GL, Zhao JH, Zhu LC. Level of vitamin K‐dependent coagulation factors in premature infants and the influence of maternal antenatal administration of vitamin K1 on their activity. Zhonghua Erke Zazhi 2005;43(12):908‐10. - PubMed

Additional references

Crowther 2010a
    1. Crowther CA, Crosby DD, Henderson‐Smart DJ. Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD000164.pub2] - DOI - PMC - PubMed
Deeks 2001
    1. Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for examining heterogeneity and combining results from several studies in meta‐analysis. Egger M, Davey Smith G, Altman DG, editor(s). Systematic Reviews in Health Care: Meta‐analysis in Context. London: BMJ Books, 2001.
Higgins 2009
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2009. Available from www.cochrane‐handbook.org.
Horbar 1992
    1. Horbar J. Prevention of periventricular‐intraventricular haemorrhage. In: Sinclair JC, Bracken MB editor(s). Effective care of the newborn infant. Oxford: Oxford University Press, 1992.
RevMan 2008 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Shearer 1992
    1. Shearer M. Vitamin K metabolism and nutriture. Blood Reviews 1992;6:92‐104. - PubMed
Thorp 1997
    1. Thorp J, Yeast J, Cohen G, Poskin M, Peng V, Hoffman E. Does in‐utero phenobarbital lower IQ? Follow up of the intracranial hemorrhage prevention trial. American Journal of Obstetrics and Gynecology 1997;176(1 Pt 2):S117.
Thorp 1999
    1. Thorp J, O'Connor M, Jones A, Hoffman E, Belden B. Does perinatal phenobarbital exposure affect developmental outcome at age 2?. American Journal of Perinatology 1999;16:51‐60. - PubMed
Thorp 2003
    1. Thorp JA, O'Connor M, Belden B, Etzenhouser J, Hoffman EL, Jones PG. Effects of phenobarbital and multiple‐dose corticosteroids on developmental outcome at age 7 years. Obstetrics & Gynecology 2003;101(2):363‐3. - PubMed
Vohr 2000
    1. Vohr BR, Wright LL, Dusick AM, Mele L, Verter J, Steichen JJ, et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Developmental Neonatal Research Network 1993‐1994. Pediatrics 2000;105:1216‐26. - PubMed

References to other published versions of this review

Crowther 1995
    1. Crowther CA, Alfirevic Z. Vitamin K prior to preterm delivery. [revised 07 April 1994]. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP, Crowther C (eds.). Pregnancy and Childbirth Module. The Cochrane Pregnancy and Childbirth Database [database on disk and CDROM]. The Cochrane Collaboration; Issue 2, Oxford: Update Software 1995.
Crowther 1997
    1. Crowther CA, Henderson‐Smart DJ. Vitamin K prior to preterm birth.. In: Neilson JP, Crowther CA, Hodnett ED, Hofmeyr GJ, Keirse MJNC (eds). Pregnancy and Childbirth Module of The Cochrane Database of Systematic Reviews, [updated 03 June 1997]. Available in The Cochrane Library [database on disk and CDROM]. The Cochrane Collaboration; Issue 3. Oxford: Update Software; 1997. Updated quarterly.
Crowther 1999
    1. Crowther CA, Henderson‐Smart DJ. Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database of Sytematic Reviews 1999, issue 2. - PubMed
Crowther 2001
    1. Crowther CA, Crosby DD, Henderson‐Smart DJ. Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database of Systematic Reviews 2001, Issue 1. [DOI: 10.1002/14651858.CD000229] - DOI - PMC - PubMed
Crowther 2010b
    1. Crowther CA, Crosby DD, Henderson‐Smart DJ. Vitamin K prior to preterm birth for preventing neonatal periventricular haemorrhage. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD000229.pub2] - DOI - PMC - PubMed

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