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Long-Term Outcomes After Neonatal Acidemia

Zaigham, Mehreen LU orcid ; Källén, Karin LU ; Sundberg, Tiia-Marie LU orcid and Olofsson, Per LU (2025) In American Journal of Obstetrics and Gynecology
Abstract

BACKGROUND: Sustained intrauterine hypoxia causes some four million perinatal deaths annually worldwide. The condition is predicated by neonatal acidemia, as determined by pH in umbilical cord blood at birth. We aimed to evaluate the association between umbilical cord arterial pH and long-term outcomes up to 20 years of follow-up.

STUDY DESIGN: Using a retrospective cohort design, umbilical cord arterial pH values from singleton births at Skåne University Hospital Malmö, Sweden, from 1997-2012 were cross-linked to data from the Swedish Medical Birth Register, Swedish Patient Register, and Cause of Death Register. The Hazard Ratio (HR) for developing disease later in life, as defined organ-wise with the International Classification... (More)

BACKGROUND: Sustained intrauterine hypoxia causes some four million perinatal deaths annually worldwide. The condition is predicated by neonatal acidemia, as determined by pH in umbilical cord blood at birth. We aimed to evaluate the association between umbilical cord arterial pH and long-term outcomes up to 20 years of follow-up.

STUDY DESIGN: Using a retrospective cohort design, umbilical cord arterial pH values from singleton births at Skåne University Hospital Malmö, Sweden, from 1997-2012 were cross-linked to data from the Swedish Medical Birth Register, Swedish Patient Register, and Cause of Death Register. The Hazard Ratio (HR) for developing disease later in life, as defined organ-wise with the International Classification of Diseases version 10 with codes 00-99, was calculated relative to umbilical cord arterial pH <7.05 and ≥7.05, respectively. In addition, umbilical cord arterial pH thresholds at 6.95, 7.00, 7.05, 7.10, 7.15, and 7.20 were evaluated for mental and behavioral disorders.

RESULTS: Of the 35931 births that met the inclusion criteria of complete and validated data, 912 (2.5%) had acidemia (umbilical cord arterial pH <7.05) at birth, while 35019 (97.5%) had non-acidemic values (pH ≥7.05). Acidemia was associated with higher mortality (P=0.043). Among groups of organ system diseases, a pH <7.05 was not associated with increased risk of disease. At the group level, the risk was not significantly increased for mental and behavioral disorders (crude HR 1.05, 95%CI 0.75-1.46), however, sub-analysis showed an increased risk of cerebral palsy (crude HR 4.30, 95%CI 2.16-8.58) and epilepsy (crude HR 1.70, 95%CI 1.02-2.86). After adjustment for maternal age, parity, smoking, body mass index, and gestational age, the associations strengthened (cerebral palsy adjusted HR 4.35, 95% CI 2.17-8.73), (epilepsy adjusted HR 1.71, 95% CI 1.02-2.88). The threshold of umbilical cord arterial pH <6.95 was significantly associated with increased risk of cerebral palsy (HR 18.38, 95%CI 7.34-46.08), epilepsy (HR 8.16, 95%CI 4.18-15.92) and intellectual disability (HR 4.19, 95%CI 1.73-10.17), whereas thresholds 7.00, 7.05, 7.10, and 7.15 were not.

CONCLUSIONS: Neonatal acidemia, defined as cord arterial pH<7.05, was associated with an increased risk of death, cerebral palsy and epilepsy, but not of other types of mental and behavioral disorders or other organ system diseases. An umbilical cord arterial pH <6.95 was significantly associated with cerebral palsy, epilepsy and intellectual disability whereas pH <7.00 and other thresholds between 7.05 and 7.20 were not.

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author
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Contribution to journal
publication status
epub
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in
American Journal of Obstetrics and Gynecology
publisher
Elsevier
external identifiers
  • scopus:105000174815
  • pmid:39983887
ISSN
1097-6868
DOI
10.1016/j.ajog.2025.02.028
language
English
LU publication?
yes
additional info
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
id
0c3fb004-26a6-46e2-9201-171c1afdfe32
date added to LUP
2025-02-25 08:06:38
date last changed
2025-07-01 07:04:39
@article{0c3fb004-26a6-46e2-9201-171c1afdfe32,
  abstract     = {{<p>BACKGROUND: Sustained intrauterine hypoxia causes some four million perinatal deaths annually worldwide. The condition is predicated by neonatal acidemia, as determined by pH in umbilical cord blood at birth. We aimed to evaluate the association between umbilical cord arterial pH and long-term outcomes up to 20 years of follow-up.</p><p>STUDY DESIGN: Using a retrospective cohort design, umbilical cord arterial pH values from singleton births at Skåne University Hospital Malmö, Sweden, from 1997-2012 were cross-linked to data from the Swedish Medical Birth Register, Swedish Patient Register, and Cause of Death Register. The Hazard Ratio (HR) for developing disease later in life, as defined organ-wise with the International Classification of Diseases version 10 with codes 00-99, was calculated relative to umbilical cord arterial pH &lt;7.05 and ≥7.05, respectively. In addition, umbilical cord arterial pH thresholds at 6.95, 7.00, 7.05, 7.10, 7.15, and 7.20 were evaluated for mental and behavioral disorders.</p><p>RESULTS: Of the 35931 births that met the inclusion criteria of complete and validated data, 912 (2.5%) had acidemia (umbilical cord arterial pH &lt;7.05) at birth, while 35019 (97.5%) had non-acidemic values (pH ≥7.05). Acidemia was associated with higher mortality (P=0.043). Among groups of organ system diseases, a pH &lt;7.05 was not associated with increased risk of disease. At the group level, the risk was not significantly increased for mental and behavioral disorders (crude HR 1.05, 95%CI 0.75-1.46), however, sub-analysis showed an increased risk of cerebral palsy (crude HR 4.30, 95%CI 2.16-8.58) and epilepsy (crude HR 1.70, 95%CI 1.02-2.86). After adjustment for maternal age, parity, smoking, body mass index, and gestational age, the associations strengthened (cerebral palsy adjusted HR 4.35, 95% CI 2.17-8.73), (epilepsy adjusted HR 1.71, 95% CI 1.02-2.88). The threshold of umbilical cord arterial pH &lt;6.95 was significantly associated with increased risk of cerebral palsy (HR 18.38, 95%CI 7.34-46.08), epilepsy (HR 8.16, 95%CI 4.18-15.92) and intellectual disability (HR 4.19, 95%CI 1.73-10.17), whereas thresholds 7.00, 7.05, 7.10, and 7.15 were not.</p><p>CONCLUSIONS: Neonatal acidemia, defined as cord arterial pH&lt;7.05, was associated with an increased risk of death, cerebral palsy and epilepsy, but not of other types of mental and behavioral disorders or other organ system diseases. An umbilical cord arterial pH &lt;6.95 was significantly associated with cerebral palsy, epilepsy and intellectual disability whereas pH &lt;7.00 and other thresholds between 7.05 and 7.20 were not.</p>}},
  author       = {{Zaigham, Mehreen and Källén, Karin and Sundberg, Tiia-Marie and Olofsson, Per}},
  issn         = {{1097-6868}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Elsevier}},
  series       = {{American Journal of Obstetrics and Gynecology}},
  title        = {{Long-Term Outcomes After Neonatal Acidemia}},
  url          = {{http://dx.doi.org/10.1016/j.ajog.2025.02.028}},
  doi          = {{10.1016/j.ajog.2025.02.028}},
  year         = {{2025}},
}