. 2010 May 13;340:c1471. doi: 10.1136/bmj.c1471

Table 1.

Studies included in systematic review of association between cord pH at birth and neonatal and long term outcomes

Studies	Risk factors	Index tests	Outcome measures
High risk population:
Baenziger et al 1999⁵⁰	All ventilated neonates; risk factors for HIE, including meconium liquor, abnormalities on cardiotocogram, low Apgar score or pH, gestation >34 weeks	Arterial cord pH <7.00	Death; hypoxic ischaemic encephalopathy (Sarnat grade >1); neurological optimality score (age 1 year); Griffiths developmental scale (age 1 year)
Beeby et al 199⁴⁴	Gestation <32 weeks; excluded congenital anomalies	Arterial cord pH <7.1	Death; cerebral palsy (age 1 year); intraventricular haemorrhage grade 3 or 4 on cranial ultrasound scan or at autopsy
Blackwell et al 2001⁵²	All neonates requiring ventilation >48 hours for meconium aspiration syndrome; gestation >37 weeks	Arterial cord pH <7.2	Seizures*
Bresadola et al 1995⁵¹	Gestation >24 weeks, <37 weeks; birth weight >700 g; excluded congenital anomalies	Arterial cord pH <7.2	Death*
Casey et al 2001⁵³	Neonates who developed respiratory symptoms postnatally; gestation >37 weeks	Arterial cord pH <7.2	Death; seizures; respiratory distress requiring ventilation; meconium aspiration syndrome
Engle 1999⁵⁶	Neonates admitted to neonatal unit directly from delivery suite; gestation >37 weeks	Arterial cord pH <7.00	Hypoxic ischaemic encephalopathy including seizures*
Ertan 2001⁹¹	Gestation 24-34 weeks	Arterial cord pH <7.10; arterial base excess >16 mmol/l	Intracranial haemorrhage (Papile, all grades) on cranial ultrasound scan*
Gaudier et al 1994⁴⁹	Birth weight 500-1000 g; gestation 23-34 weeks; excluded congenital anomalies	Arterial cord pH <7.05	Wechsler intelligence scale for children (IQ <70); cerebral palsy (chronic non-progressive motor disability characterised by abnormal posture and movements), follow-up to age 7 years; motor or mental deficit severe enough to interfere with normal function, including one or more of mental retardation, cerebral palsy, deafness, blindness, or hydrocephaly
Gea 2007⁹³	Birth weight <2000 g; gestation <37 weeks; excluded congenital anomalies, maternal diabetes, and rhesus incompatibility	Venous cord pH <7.20; venous base excess >10 mmol/l	Periventricular or intraventricular haemorrhage on cranial ultrasound scan; ventilation >24 hours; necrotising enterocolitis (Bell grade 2)*
Gonzalez de Dios et al 2000⁵⁹	At least one risk factor for asphyxia (for example, Apgar score <6, cord pH <7.00, antenatal risk factors); excluded if congenital anomaly, sepsis, metabolic disorder, postnatal depression; gestation >37 weeks	Arterial cord pH ≤7.00	Serum creatinine level >1.2 mg/dl; hypoxic ischaemic encephalopathy (Levine’s criteria, all grades); abnormal neurological status (Amiel-Tison criteria), age 2 years
Graham et al 2004⁶¹	Gestation 23-34 weeks	Arterial cord pH <7.00	Periventricular leucomalacia or ventricular dilatation on cranial ultrasound scan*
Haddad et al 2000⁶²	Neonates with Apgar score 0 at 1 and 5 minutes, resuscitated and transferred to neonatal unit; excluded congenital malformations, chromosome abnormalities, birth before arrival; gestation 25.5-42.1 weeks	Arterial cord pH <7.00	Death; hypoxic ischaemic encephalopathy
Hernandez et al 1993⁶³	Clinical and radiological evidence of meconium aspiration syndrome; excluded if congenital anomalies, cytomegalic inclusion disease, delivery outside hospital	Arterial cord pH <7.00, <7.10, and <7.20	Ventilation required; ventilation ≥3 days
Hibbard et al 1991⁶⁴	Birth weight 500-1500 g	Arterial cord pH ≤7.05 and ≤7.15	Death; intraventricular haemorrhage (Papile grade 1-4) on cranial ultrasound scan; abnormal neurological status defined as seizures, cortical atrophy, need for shunt placement; hyaline membrane disease (chest radiography); bronchopulmonary dysplasia (chest radiography); necrotising enterocolitis
Holmes et al 2001⁶⁶	Birth weight 750-2500 g; gestation 25-35 weeks; excluded if caesarean section before labour, congenital anomalies, uninterpretable fetal heart rate trace	Arterial cord pH <7.10	Death; intraventricular haemorrhage (Papile grade 3 or 4); periventricular leucomalacia*
Kato 1997⁵	Birth weight <1500 g. Congenital anomalies excluded	Arterial cord pH <7.20	Death*; cerebral palsy or mental retardation (at least 12 months old)
Loh et al 1998⁷²	Included if one or more of following risk factors: abnormality on cardiotocogram, scalp pH<7.25, thick meconium or no liquor, cord prolapse or bradycardia, antepartum haemorrhage, estimated fetal weight <1500 g, gestation <34 weeks, breech, poorly controlled type 1 diabetes, pre-eclampsia, suspected fetal anomalies, transverse or oblique lie at caesarean section, multiple pregnancies	Arterial cord pH <7.00	Hypoxic ischaemic encephalopathy
Luthy et al 1987⁷⁴	Gestation 26-32 weeks; excluded multiple pregnancy, non-cephalic presentation, malformations, delivery before labour, antenatal haemorrhage	Arterial cord pH ≤7.20	Death; cerebral palsy (age 18 months); intraventricular haemorrhage on cranial ultrasound scan (Papile grade 3 or 4)*
Murphy et al 1995⁷⁵	Gestation 23-32 weeks; excluded multiple pregnancy	Arterial cord pH ≤7.10	Cerebral palsy (permanent impairment of voluntary movement or posture), age unreported
Salafia et al 1995⁷⁸	Gestation <32 weeks; excluded if congenital anomalies, multiple pregnancy, maternal diabetes mellitus or chronic hypertension, fetal hydrops, placenta praevia, intrauterine growth restriction	Arterial cord pH <7.10; venous cord pH <7.10	Germinal matrix or intraventricular haemorrhage diagnosed on cranial ultrasound scan (grade 1-4)*
Socol 1994⁸¹	Apgar score ≤3 at 5 minutes; excluded birth weight <2000 g and gestation <34 weeks	Arterial cord pH <7.00; arterial base excess >12 mmol/l	Cerebral palsy or motor deficit (age 1-7 years); seizures; renal impairment (serum creatinine level >1.5 mg/dl, or oliguria); cognitive impairment on Wechsler scale (cut off <70), age 1-7 years
Spinillo et al 1995⁸²	Birth weight <2500 g	Arterial cord pH <7.20	Bayley index abnormal (71-84), age 2 years
Tejani and Verma 1989⁸³	Birth weight ≤2000 g; excluded major congenital anomalies	Arterial cord pH ≤7.10	Death; intraventricular haemorrhage on cranial ultrasound scan (Papile grade 1-4); respiratory distress syndrome (radiological evidence of reticulogranular pattern and air bronchograms)*
Yudkin et al 1994⁸⁹	Apgar score ≤3 at 1 minute; gestation >37 weeks; excluded multiple pregnancies and death related to congenital anomaly or rhesus disease	Arterial cord pH <7.15	Death*; any impairment (age 5 years); serious impairment (global delay, lateralising signs and severe deficit in a specific area), age 5 years
Yoon et al 1996⁸⁸	Gestation 25-36 weeks; excluded major congenital malformations or death before examination	Arterial cord pH <7.15	Periventricular leucomalacia on cranial ultrasound scan or at autopsy*
Unselected or low risk population:
Dennis et al 1989⁵⁴	Gestation >37 weeks; singletons surviving to age 4.5 years	Arterial cord pH ≤7.10; arterial base excess >12 mmol/l	Griffiths developmental scales age 4.5 years: locomotor, personal or social, hearing and speech, performance, and overall impairment
Dijxhoorn et al 1986⁴¹	Gestation >37 weeks; excluded caesarean delivery or breech presentation	Arterial cord pH ≤7.10 and ≤7.20	Neurological status (abnormal if one of hyperkinesias or hypokinesia, hypertonia or hypotonia, hemisyndrome, apathy syndrome, or hyperexcitability syndrome)*
D’Souza et al 1983⁵⁵	Normal pregnancy, vaginal delivery 39-42 weeks	Venous cord pH <7.27	Neurological status (abnormal if one of hypotonia, lethargy, feeding difficulties, jittery)*
Ghosh et al 2003⁵⁷	Gestation >37 weeks; singletons excluded if rhesus isoimmunisation, maternal anaemia, or diabetes mellitus	Arterial cord pH ≤7.15	Hypoxic ischaemic encephalopathy; death
Gilstrap et al 1989⁵⁸	Gestation >37 weeks, cephalic presentation, birth weight >2500 g; excluded congenital anomalies	Arterial cord pH <7.00	Hypotonia >24-48 hours; respiratory distress requiring oxygen; seizures*
Graham 2002⁶⁰	Excluded congenital anomalies	Arterial cord pH <7.00	Seizures*
Heller et al 2003¹	Excluded congenital anomalies	Arterial cord pH ≤7.00, ≤7.10, and ≤7.20	Death*
Hogan 2007⁶⁵	Gestation >37 weeks	Arterial cord pH ≤7.15	Composite reference standard hypoxic ischaemic encephalopathy (Sarnat, all grades) or hypoxic death*
Huisjes and Aarnoudse 1979⁶⁷	Population characteristics unreported	Arterial cord pH ≤7.09	Abnormal neonatal neurological status (Prechtl method)*
Ingemarrson et al 1997⁶⁸	Population characteristics unreported	Arterial cord pH <7.05 and <7.00	Death; cerebral palsy (age 4 years); impact of events scale (Sarnat grade 1-3); attention deficit (age 4 years); speech difficulty (age 4 years); motor delay (age 4 years)
Jurgens- van der Zee et al 1979⁶⁹	Neonates; excluded if neonatal death or parents refused examination	Venous cord pH <7.20	Abnormal neurological examination result (Prechtl method): 1 or more of increased or decreased excitability including seizures, apathy or coma; abnormal motility or tone; peripheral or central nervous system lesions*
Larma et al 2007⁷⁰	Gestation ≥24 weeks	Arterial cord pH <7.00	Seizures; periventricular leucomalacia; intraventricular haemorrhage; respiratory dysfunction; renal dysfunction* (thresholds unreported)
Litschgi et al 1974⁷¹	Population characteristics unreported	Arterial cord pH <7.09	Abnormal neurological examination result (24 hours after birth)*
Low 1997⁷³	Gestation ≥37 weeks	Arterial base excess >12 mmol/l	Composite outcome score; neurological abnormality (lethargy, abnormal tone, coma, or seizures); respiratory dysfunction (continuous positive airway pressure or ventilation required); cardiovascular dysfunction (hypotension, hypertension, abnormal electrocardiogram or echocardiogram); renal dysfunction (serum creatinine level >100 umol/l, anuria, or oliguria <1 ml/kg/h)*
Perlman and Risser 1996⁷⁶	Gestation ≥37 weeks	Arterial cord pH ≤7.00	Seizures*
Sakuraba and Saling 1989⁷⁷	Population characteristics unreported	Arterial cord pH ≤7.19 and ≤7.24	Intracranial haemorrhage diagnosed on cranial ultrasound scan*
Schneider and Tanner 1985⁷⁹	Twins only included	Arterial cord pH <7.20	Binet Simon Kramer (intelligence); language test; emotional intelligence test; Raven intelligence test (non-spoken); neurological status (all tests carried out at age 5-7 years)
Silva et al 2008⁸⁰	Gestation ≥34 weeks; excluded congenital malformations and chromosome anomalies	Arterial cord pH <7.00 and <7.10	Hypotonia at birth necessitating admission to neonatal unit; hypoxic ischaemic encephalopathy; seizures*
Svirko et al 2008⁹²	Gestation ≥36 weeks; one of reference tests done and cord pH available; excluded if delivered by prelabour elective caesarean section	Arterial cord pH <7.10	Wechsler objective reading dimensions (age 6-8 years); test for comprehension of grammar (age 5-7 years); Naglieri non-verbal ability (age 6-8 years); cut off <100 age standardised score used for all tests
Thoulon et al 1972⁸⁴	Population characteristics unreported	Venous cord pH <7.20	Death*; abnormal neurological examination (age 18 months)
Valentin et al 1993⁸⁵	Anomalies not excluded	Arterial cord pH ≤7.00 and ≤7.10; venous cord pH ≤7.10 and ≤7.20	Composite measure of neonatal sequelae, including severe symptoms requiring treatment (for example, ventilation, intravenous fluids), death, or survival with sequelae*
Van den Berg 1996¹⁰	Excluded chromosomal or major congenital anomalies or intrauterine infection	Arterial cord pH <7.00 (compared with group of neonates with cord pH >7.24)	Seizures; intracranial haemorrhage on cranial ultrasound scan; periventricular leucomalacia on cranial ultrasound scan; renal impairment (serum creatinine level >90µmol/l); abnormal liver function (aspartate transaminase level >33 U/l, alanine aminotransferase level >25 U/l); necrotising enterocolitis (criteria unreported)
Vintzileos et al 1993⁹⁰	Gestation ≥26 weeks; excluded known congenital or chromosomal anomalies	Arterial cord pH <7.10	Death*
Wildshut et al 2005¹¹	Gestation 37-42 weeks; neonates included if growth between 2.3 and 97.7th centiles, vertex position, stay in hospital at least 3 days after birth; excluded if hypoxia ischaemia other than caused by perinatal adverse conditions. Exclusions included meconium aspiration, respiratory distress syndrome, infection, birth after complicated pregnancy, congenital malformations, maternal medication, alcohol or drug misuse, metabolic disorders	Arterial cord pH <7.10	Movement ABC test (score <16 or unable to perform due to movement disorder), age 4 years
Winkler 1991⁸⁶	Gestation ≥37 weeks	Arterial cord pH <7.20	Composite reference standard: seizures or neonatal death*
Wu et al 1998⁸⁷	Gestation ≥37 weeks; singletons only	Arterial cord pH <7.19	Motor delay; speech delay; difficulty concentrating (all assessed age 4 years)

*Outcomes within neonatal period.