Table S1. Important Characteristics of Studies of ID

Table S1. Important characteristics of studies of ID

Study, year / Location / Sample / Criteria / Cases/ controls b / Control / Hypoxia/ Asphyxia proxies / Selection / Comparability / Exposure/ Outcome
Akesson 1966 / Stockholm, Uppsala/Sweden / P / SB IQ<85 / 349 / 698 / Two subjects of the same sex born after / Undefined asphyxia/hypoxia (3.61, 2.01-6.46) / 4 / 1 / 2
Atladottir et al 2015 / Denmark / P / IQ<70 (several measures) / 6590 / 1099044 / All the rest of the population / RDS (2.69, 2.25-3.20) / 4 / 2 / 3
Benaron et al 1960a / Chicago/US / C / SB IQ<70 / Apnea30 b / 40 / Those whose mother experienced natural labor / Apnea (9.75, 1.10-86.01) / 4 / 0 / 3
Bilder et al 2013 / UT/US / P / IQ<70 (several measures) / 146 / 16936 / Gender and Birth year matched / 5 min Apgar (10.48, 5.68-19.35), O2 ventilation (8.78, 4.77-16.15) / 4 / 2 / 3
Camp et al 1998 / Several cohorts in the US / P / WISC IQ<70 / 1419 / 34265 / All the rest of the population without exposure / 1 min Apgar (1.66,1.01-2.71), Apnea (2.05, 1.29-3.28) / 4 / 0 / 2
Campbell et al 1950 / Belfast/ Ireland / C / Raven IQ (cutoff unavailable) / Asphyxia61 b / 134 / Records before and after each asphyxia record / Undefined asphyxia/hypoxia (0.83, 0.33-2.10) / 4 / 1 / 2
Cans et al 1999 / France / P / WISC-R IQ<70 / 144 / 864 / Birth place and Birth year matched / 5 min Apgar (2.95,1.79-4.86), O2 ventilation (3.32, 2.21-4.99), Acidosis (3.48, 2.24-5.41) / 4 / 2 / 3
Chapman et al 2008 / FL/US / P / IQ<70 (Several measures) / 7054 / 266513 / All the rest of the population (excluding ASD and other learning disabilities) / 5 min Apgar (<4, 6.48, 4.97-8.46; <7, 5.02, 4.42-5.69) / 4 / 0 / 3
Corah et al 1965 a / Washington/US / C / WISC IQ (cutoff unavailable) / Anoxia
99 b / 133 / Age, race, Sex, Social class matched / Undefined asphyxia/hypoxia / 4 / 2 / 3
Darke 1944 a / NY, PA/ US / C / SB IQ<70 / Asphyxia 19 b / 19 / Parent or sibling / Undefined asphyxia/hypoxia (4.80, 0.48-47.68) / 3 / 0 / 2
Drage et al 1969 a / US / P / SB IQ (cutoff unavailable) / 5 min Apgar<7
843 b / 17195 / All the rest of the population / 5 min Apgar / 2 / 1 / 1
Dweck et al 1974 / Birmingham/UK / C / SB or Cattell Infant Intelligence Scale IQ<80 / Asphyxia 15 b / 15 / Same population but unmatched / 1 min Apgar (8.68, 0.41-184.28), Acidosis (8.68,0.41-184.28) / 4 / 0 / 2
Ehrestein et al 2009 a / Denmark / P / Boerge
Prien test IQ (cutoff unavailable) / 5min Apgar<7
106 b / 17105 / All the rest of the population / 5 min Apgar (1.74, 0.80-3.80) / 4 / 0 / 3
Fisch et al 1975 / US / P / SB IQ (cutoff unavailable) / 57 RDS b / 35188 / Those without RDS, matched for hospital, birth weight, socioeconomic status, gestational age, race / RDS (2.35, 1.28-4.29) / 4 / 2 / 3
Gillberg et al 1990 / Goteborg/Sweden / P / WISC, Terman-Merrill test IQ<70 / 130 / 130 / Birth year and gender matched in the same obstetric department / O2 ventilation (3.64, 0.74-17.88), RDS (5.92, 1.28-27.24) / 4 / 0 / 3
Graham et al 1962 a / MO/US / C / SB IQ<73 / Anoxia 114 b / 158 / Age, race, sex, social class matched / Undefined asphyxia/hypoxia (3.40, 0.86-13.45) / 4 / 2 / 3
Handley-Derry et al 1997 a / Ontario/Canada / C / WISC IQ (cutoff unavailable) / Asphyxia 36 b / 30 / Age, GA, and birth weight matched / Acidosis / 3 / 2 / 3
Jonas et al 1989 / South Australia / P / IQ (measure, cutoff unavailable) / 113 / 982 / Random from the same population / 5 min Apgar (4.92, 1.92-12.61), O2 ventilation (2.88, 1.20-6.90), apnea (3.85, 2.17-6.81) / 3 / 0 / 3
Kamper 1978a / Denmark / C / WISC, WPPSI IQ<85 / RDS+ ventilation
52 b / 58 / Age, gender, GA, and birth weight, SES, birth order matched / O2 ventilation and RDS (6.67, 0.75-59.21) / 4 / 2 / 2
Lamont et al 1988 / Southampton/UK / C / IQ<85 (measure unavailable) / 120 / 120 / Sibling / 5 min Apgar (2.32, 0.78-6.90) / 3 / 0 / 3
Langridge et al 2013 / Western Australia / P / IQ<70 (Several measures) / 4576 / 376529 / All the rest of the population / Resuscitation (1.56,1.47-1.65) / 4 / 2 / 3
Lawlor et al 2006 a / Brisbane/Australia / P / Raven’s SPM (cutoff unavailable) / 5 min Apgar<9
211 b / 3367 / All the rest of the population without exposure / 1 and 5 min Apgar / 4 / 0 / 3
Louhiala et al 1995 / Southern and Central Finland / P / IQ<71 (measure unavailable) / 339 / 339 / Covering the birth year of the case child from the hospital delivery book / 5 min Apgar (7.83, 2.72-22.54), 1 min Apgar (5.51, 2.90-10.47) / 4 / 2 / 2
Odd et al 2009 a / Bristol/UK / P / WISC-III IQ<80 / Resuscitation
426 b / 5461 / All the rest of the population without exposure / Resuscitation (1.70, 1.23-2.36) / 4 / 2 / 2
Rantakallio et al 1985 / Northern Finland / P / IQ <86 (Several measures) / 326 / 11320 / All the rest of the population / Undefined asphyxia/hypoxia (5.69, 2.98-10.86) / 4 / 0 / 2
Robertson et al 1993 a / Canada / C / WISC IQ (cutoff unavailable) / HIE
122 b / 130 / Peer, newborn / Asphyxia as HIE / 4 / 0 / 3
Schreiber et al 1943 / MI/US / C / IQ (measure, cutoff unavailable) / 100 / 100 / Age, SES, birth place / Undefined asphyxia/hypoxia (4.94,1.92-12.72) / 3 / 1 / 3
Seidman 1991 a / Jerusalem/ Israel / P / Verbal Otis and Nonverbal matrices test<85 / 5 min Apgar<8
46 b / 1896 / All the rest of the population without exposure / 5 min Apgar (0.60, 0.14-2.49), 1 min Apgar (1.13, 0.60-2.15) / 4 / 0 / 3
Sonnander et al 1987 / Uppsala/Sweden / C / IQ <70 (measure unavailable) / 15 / 72 / Controls from the same population / Resuscitation (15.00, 0.58- 386.81), Apnea 15.00, 0.58- 386.81) / 2 / 0 / 3
Stromme et al 2000 / Akershus/Norway / P / IQ<70 (Several measures) / 178 / 29859 / All the rest of the population / 5 min Apgar (<3, 3.48, 2.24-5.41;<7, 7.33, 3.93-13.65), 1 min Apgar (<3,7.95, 3.67-17.21; <7, 2.61,1.63-4.17) / 4 / 0 / 3
Sussmann et al et al 2009 / Scotland / C / WISC-III-R or WAIS<70 / 49 / 41 / Volunteers and siblings / Resuscitation (1.89, 0.64-5.59), 5 min Apgar (3.56, 0.38-33.14) / 2 / 0 / 3
Taylor et al 1985 / Dundee/Scotland / C / IQ (measure, cutoff unavailable) / 25 / 600 / Records before and after each neurodevelopmental disability record / O2 ventilation (5.04, 1.99-12.72), 1 min Apgar (2.76, 1.12-6.84), 5 min Apgar (11.24, 3.26-38.78) / 3 / 0 / 3
Thorngren-Jerneck et al 2001 / Sweden / P / IQ (several measures) / Total
1028705 / All the rest of the population / 5 min Apgar (9.50, 7.21-12.52) / 4 / 0 / 3
Usdin and Well 1952 a / Cincinnati/US / C / SB IQ<70 / Apnea
41 b / 43 / Matched for Social class and age, No neurological finding or prematurity / Apnea (0.20, 0.01-4.29) / 4 / 0 / 2
Van Handel et al 2007 a / Utrecht/Netherland / C / WISC-III IQ / 80 HIE b / 46 / Age and gender matched / Asphyxia as HIE / 4 / 2 / 1
Von Wendt et al 1987 / Finland / P / IQ (several measures) (cutoff unavailable) / 66 / 11732 / All the rest of the population / 1 min Apgar (1.41, 0.56-3.52) / 3 / 0 / 3

Abbreviations: C, clinic-based; DSM-IV-TR, Diagnostic and Statistical Manual-IV –Text Revision; HIE, hypoxic ischemic encephalopathy; ICD, International Classification of Disease; IQ, intelligence quotient; P, population-based; SB, Stanford Binet; SPM, Standard Progressive Matrices; WISC, Wechsler Intelligence Scale for Children; WPPSI, Wechsler Preschool and Primary Scale of Intelligence

a Used for comparison of IQ scores between exposed and unexposed groups.

b Number of cases and controls reflect the values in exposed/nonhypoxicgroups

Table S2. Important characteristics of studies of ASD

Study, year / Location / Sample / Diagnosis / Cases/ controls number / Control / Proxies of impaired gas exchange (OR, 95%CI) / Selection / Comparability / Exposure/ Outcome
Atladottir et al 2015 / Denmark / P / IQ<70 (several measures) / 6590 / 1099044 / All the rest of the population / RDS (1.41,1.16-1.71) / 4 / 2 / 3
Bilder et al 2009 / UT/US / P / DSM-IV-TR / 132 / 13200 / Gender and Birth year matched / 5 min Apgar (0.78, 0.19-3.17), RDS (0.49,0.07-3.51), O2 ventilation (0.42, 0.06-3.04) / 4 / 2 / 3
Buchmayer et al 2009 / Sweden / P / ICD-9,10 / 1216 / 6080 / Gender birth year, birth hospital matched / 5 min Apgar (2.22, 1.46-3.38) RDS (1.43,1.06-1.93) / 4 / 2 / 3
Burd et al 1999 / ND/US / P / DSM-III,IIIR,IV / 49 / 245 / Gender, birth year and month matched / 1 min Apgar (1.98, 0.82-4.74), 5 min Apgar (2.24, 0.87-5.72) / 4 / 2 / 2
Burstyn et al 2010 / Alberta/ Canada / P / ICD-9 / 1138 / 218890 / All the rest of the population / 1 min (1.50, 1.30-1.73), 5 min Apgar (1.61, 1.14-2.27) / 3 / 2 / 3
Burstyn et al 2011 / Alberta/ Canada / P / ICD-9 / 643 / 104993 / All the rest of the population / Acidosis (1.11, 0.90-1.36) / 3 / 2 / 3
Cassimos et al 2015 / Greece / P / Not mentioned / 273 / 273 / Matched for age / 5 min Apgar (2.48, 1.07-5.76) / 2 / 1 / 1
Comi et al 1999 / TN/US / C / Not mentioned b / 61 / 46 / Local pediatric practice / Undefined asphyxia/hypoxia (5.83, 0.69-49.20) / 2 / 0 / 2
Deykin et al 1980 / MA/US / C / c / 118 / 246 / Siblings / Delayed crying (3.24, 0.90-11.71) / 4 / 2 / 3
Dodds et al 2011 / Nova Scotia/ Canada / P / ICD-9,10 / 919 / 128205 / All the rest of the population / 5 min Apgar (1.59, 0.97-2.61), RDS (2.10,1.33-3.32) / 4 / 0 / 3
Duan et al 2014 / Zhengzhou/ China / C / DSM-IV / 286 / 286 / Gender matched / Undefined asphyxia/hypoxia (12.20, 4.79-31.06) / 4 / 2 / 2
Finegan and Quarrington 1979 / Toronto/ Canada / C / A 4-item criteria / 15 / 15 / Siblings / O2 ventilation (5.74, 0.25-130.37), RDS (8.68, 0.41-184.28) / 3 / 0 / 2
Froehlich-Santino et al 2014 / CA/US / P / ADI-R, ADOS / 297 / 133 / Twins / Undefined asphyxia/hypoxia (1.71, 1.08-2.71), O2 ventilation (1.96, 1.17-3.27), RDS (2.11,1.27-3.51) / 4 / 2 / 3
Gillberg et al 1983 / Goteborg/ Sweden / C / d / 25 / 25 / Gender matched / O2 ventilation (3.40, 0.13-87.72), RDS (1.09, 0.06-18.51) / 4 / 2 / 3
Glasson et al 2004 / Western Australia / P / DSM / 465 / 1313 / Gender matched / Apnea (1.40, 1.03-1.89), 1 min Apgar (2.48, 1.70-3.62) / 4 / 2 / 3
Khaiman et al 2015 / Thailand / C / DSM-IV-TR / 215 / 234 / Age matched / Undefined asphyxia/hypoxia (0.65, 0.15-2.74) / 2 / 2 / 1
Langridge et al 2013 / Western Australia / P / DSM-III-TR, IV, IV-R / 1179 / 376529 / All the rest of the population / Resuscitation (1.22,1.08-1.37) / 4 / 2 / 3
Larsson et al 2005 / Denmark / P / ICD-8 and 10 / 698 / 17450 / Gender, birth year, age matched / 5 min Apgar (2.64, 1.61-4.32) / 4 / 2 / 3
Lord et al 1989 / NC/US-Alberta/Canada / C / ADI, DSM-III-TR / 46 / 54 / Siblings / RDS, (4.13, 1.05-16.33) O2 ventilation (2.51, 1.03-6.11) / 2 / 0 / 2
Maimburg et al 2006 / Denmark / P / ICD-8 and 10 / 473 / 4730 / Sex, year, county of birth matched / Acidosis (1.06, 0.72-1.55) / 4 / 2 / 3
Mamidala et al 2013 / India / C / ICD-10 and DSM-IV / 471 / 471 / Age and gender matched / Undefined asphyxia/hypoxia (11.82, 4.68-29.84), delayed crying (4.34, 1.76-10.69) / 4 / 2 / 3
Marmara et al 2014 / NJ/US / C / DSM-IV-TR / 263 / 115632 / General population / Undefined asphyxia/hypoxia (7.28, 4.49-11.78) / 3 / 0 / 0
Mason-Brothers et al 1990 / UT/US / P / DSM-III / 175 / 55 / Siblings / 1 min Apgar (<5, 0.55, 0.19-1.56; <7, 0.86, 0.40-1.85)), 5 min Apgar (<4, 0.72, 0.06-8.16; <7, 0.90, 0.33-2.45), O2 ventilation (1.56, 0.69-3.55) / 4 / 1 / 3
Mrozek-Budzyn et al 2013 / Voivodeship/Poland / P / ICD-10 / 96 / 192 / year of birth, gender, outpatient clinic matched / O2 ventilation (2.35, 1.09-5.11), 5 min Apgar (<5, 2.02, 0.13-32.67; <1.34, 0.22-8.16; <9, 1.85, 0.92-3.72), RDS (2.20, 1.05-4.61) / 4 / 2 / 2
Nath et al 2012 / Kolkata/ India / C / DSM-IV-TR / 31 / 100 / Age matched / Undefined asphyxia/hypoxia (0.62, 0.13-3.00) / 2 / 1 / 2
Piven et al 1993 / Baltimore/ US / C / ICD-10 / 39 / 39 / Siblings / O2 ventilation (5.27, 0.24-113.35), 5 min Apgar (1.58, 0.53-4.68), RDS (3.08, 0.12-77.90) / 3 / 0 / 2
Polo-Kantola et al 2014 a / Finland / P / ICD-9,10 / 4104 / 16344 / Sex, date of birth, and place of birth matched / 1 min Apgar (<7, 1.32, 1.13-1.53; <9, 1.25, 1.16-1.35) / 4 / 2 / 3
Steffenburg et al 1989 / Scandinavia / C / DSM-III-R / 21 / 21 / Twins / O2 ventilation (5.64, 0.29-108.71), RDS (0.11, 0.004-2.85) / 4 / 2 / 3
Stein et al 2006 / Tel Aviv/Israel / P / ICD-8, DSM-III, III-R, IV / 206 / 152 / Children of medical center workers / Apnea (2.99,1.26-7.09) / 3 / 0 / 2
Sugie et al 2005 / Hamatsu/ Japan / C / DSM-IV / 225 / 1580 / Normal children within the same age range / Undefined asphyxia/hypoxia (8.19, 3.13-21.45), RDS (1.41, 0.48-4.18) / 3 / 0 / 2
Visser et al 2013 / Nijmegen/ Netherland / C / ADOS, DSM-IV-TR / 204 / 322 / Gender and region matched / Undefined asphyxia/hypoxia (2.66, 1.25-5.66) / 4 / 2 / 3
Williams et al 2008 / NSW/ Australia / P / DSM-IV / 181 / 85529 / All the rest of the population / 1 min Apgar (1.70, 1.10-2.63), 5 min Apgar (1.47, 0.36-5.95) / 4 / 0 / 2
Zhang et al 2010 / Tianjin/China / P / ICD-10 / 95 / 95 / Birth year and gender matched / Apnea (12.31,1.56-97.37) / 3 / 2 / 2

Abbreviations: ADI-R, Autism Diagnostic Interview-Revised; ADOS, Autism Diagnostic Observation Schedule; CARS, Childhood Autism Rating Scale; C, clinic-based; DSM-IV-TR, Diagnostic and Statistical Manual-IV –Text Revision; ICD, International Classification of Disease; P, population-based

athis study was included as three separate studies in the meta-analysis, because case and controls for each group were separate

b Patients were part of "east Tennessee Chapter of the Autism Society of America"

cImpairment in any of the three areas of impaired relatedness to the environment

dearly onset (before 2.5 years of age) disturbance of ability to relate to people in combination with severe speech-language disorder and behavior problems (stereotyped mannerisms, severe ritualistic traits, or insistence on sameness)

4 (a) onset prior to 30 months of age,(b) disturbance of ability to relate to people, (c) disturbance in the use of language, and (d) the existence of a restricted repertoire of behaviors, such as insistence on sameness and ritualistic, restricted play

Figure S1. Flowchart of study selection

Figure S2. Differences in IQ with relation to presence or absence of proxies of impaired gas exchange