TABLE 1

Characteristics of Studies Included in the Systematic Review

First Author, Year (Country)Design (Sample Size)OutcomeInterval Used; Interval Categories, moConfounding/Mediating FactorsMain Findings
Autism Spectrum Disorder
 Cheslack-Postava,28 2011 (United States)Cross-sectional, population-based (662 730 children)Autistic disorder (according to case files of the Department of Developmental Services; Asperger disorder and PDD-NOS were not included)IPI; <12, 12–23, 24–35, 36–47, 48–59,a 60–71, 72–83, >84; and <12, 12–23, 24–35, ≥36aMaternal and paternal age, race/ethnicity, maternal education, mother’s birthplace, payment source for delivery, child’s gender, birth year, preterm birth, low birth weightIntervals <36 mo were associated with increased risk of autistic disorder (aOR 3.39, 95% CI 3.00–3.82 for intervals <12 mo; aOR 1.86, 95% CI 1.65–2.10 for intervals 12–23 mo; and aOR 1.26, 95% CI 1.10–1.45 for intervals 24–35 mo). No relationship between intervals ≥60 mo and autistic disorder.
 Dodds,29 2011 (Canada)Cohort population-based (129 733 children)ASD (ICD-9 code 299 or ICD-10 code F84)IPI; <18, ≥18aSeveral maternal sociodemographic and obstetric factors; maternal conditions including psychiatric and neurologic disorders; income, factors related to labor/delivery; several perinatal factors including gestational age, birth weight, and infant gender; neonatal morbidities including anomalies, breastfeeding at discharge, sibling with autism, birth yearIntervals <18 mo were associated with increased risk of ASD (aRR 1.51, 95% CI 1.12–2.03).
 Gunnes,30 2013 (Norway)Cross-sectional, nation-based (223 476 children)ASD (ICD-10 codes F84.0, F84.1, F84.5, F84.8, and F84.9), autistic disorder (ICD-10 code F84.0), and Asperger disorder (ICD-10 code F84.5) plus PDD-NOS (ICD-10 codes F84.1, F84.8, and F84.9) at age 8 yIPI; <9, 9–11, 12–23, 24–35, ≥36aMaternal and paternal age, maternal education, child’s gender, birth year, preterm birth of the first-born childIntervals <12 mo were associated with increased risk of autistic disorder (aOR 2.18, 95% CI 1.42–3.26 for intervals <9 mo; and aOR 1.71, 95% CI 1.07–2.64 for intervals 9–11 mo). Intervals of 9–11 mo were associated with increased risk of ASD (aOR 1.35, 95% CI 1.05–1.73). No relationship between intervals <24 mo and Asperger disorder and PDD-NOS.
 Cheslack-Postava,31 2014 (Finland)Nested case-control population-based (2208 children with diagnosis of ASD and 5163 controls)ASD (ICD-10 codes F84.0, F84.5, F84.8, and F84.9), autistic disorder (ICD-10 code F84.0), Asperger disorder (ICD-10 code F84.5), and PDD-NOS (ICD-10 codes F84.8 and F84.9)IPI; <12, 12–23, 24–59,a 60–119, and ≥120Maternal and paternal age, parental psychiatric disorders, parity, previous miscarriage/abortions, any ASD diagnosis in a previous sibling, maternal socioeconomic status, previous miscarriage or abortion, date of birth, place of birth, infant gender, residence, preterm birth, low birth weightIntervals <12 and ≥60 mo were associated with increased risk of ASD (aOR 1.50, 95% CI 1.28–1.74 for intervals <12 mo; aOR 1.28, 95% CI 1.08–1.52 for intervals 60–119 mo; and aOR 1.44, 95% CI 1.12–1.85 for intervals ≥120 mo). Only intervals <24 mo were associated with increased risk of autistic disorder (aOR 1.89, 95% CI 1.42–2.50 for intervals <12 mo; aOR 1.51, 95% CI 1.18–1.94 for intervals 12–23 mo). Only intervals <12 mo were associated with increased risk of PDD-NOS (aOR 1.55, 95% CI 1.22–1.97). Only intervals ≥60 mo were associated with increased risk of Asperger disorder (aOR 1.55, 95% CI 1.15–2.08 for intervals 60–119 mo; and aOR 1.71, 95% CI 1.13–2.60 for intervals ≥120 mo).
 Coo,32 2015 (Canada)Cohort population-based (41 050 children)ASD (ICD-9 codes 299, 299.0, 299.8, and 299.9; ICD-10 codes F84.0, F84.1, F84.5, F84.8, and F84.9; or an ASD diagnosis in the Education or Children’s Special Services databases)IPI; <12, 12–23, 24–35, ≥36aChild’s gender, birth year, presence of an intellectual disability, maternal age at delivery, and whether the mother had ever received income assistanceThere was no significant association between IPI and ASD (aOR 1.72, 95% CI 0.96–3.06 for intervals <12 mo; aOR 1.59, 95% CI 0.93–2.71 for intervals 12–23 mo; and aOR 1.29, 95% CI 0.70–2.38 for intervals 24–35 mo)
 Durkin,33 2015 (United States)Cohort population-based (31 467 children)ASD (according to the American Psychiatric Association’s DSM-IV-TR criteria for a pervasive developmental disorder, including autistic disorder, Asperger disorder, or PDD-NOS), autistic disorder, and Asperger disorder plus PDD-NOS at age 8 yIPI; <12, 12–23, 24–47,a 48–59, 60–83, ≥84; and <12, 12–23, 24–35, ≥36aMaternal and paternal age, maternal education, child’s gender, birth year, first trimester prenatal care, history of pregnancy loss, low birth weight, preterm birth, small for gestational age, gestational diabetes, cesarean deliveryIntervals <12 and ≥84 mo were associated with increased risk of ASD (aOR 2.16, 95% CI 1.32–3.53 for intervals <12 mo; and aOR 1.98, 95% CI 1.12–3.48 for intervals ≥84 mo). Only intervals <24 mo were associated with increased risk of autistic disorder (aOR 2.75, 95% CI 1.56–4.84 for intervals <12 mo; and aOR 1.80, 95% CI 1.07–3.03 for intervals 12–23 mo). Intervals ≥84 mo were associated with marginally significant increased risk of Asperger disorder and PDD-NOS (aOR 2.72, 95% CI 0.99–7.49).
 Zerbo,34 2015 (United States)Cross-sectional (44 383 children)ASD (ICD-9 codes 299.0, 299.8, and 299.9, and according to case files of the Department of Developmental Services)IPI; <6, 6–8, 9–11, 12–23, 24–35, 36–47,a 48–59, 60–71, ≥72; and <12, 12–23, 24–35, ≥36aMaternal and paternal age, child′s gender, year of birth, maternal education, mother′s race/ethnicity, place of birth, maternal BMI, change in BMI between pregnancies, maternal antidepressant use in the 3 mo before conception, ASD status of the first child, and birth weight, gestational age, and type of delivery of both first- and second-born childIntervals <24 and ≥72 mo were associated with increased risk of ASD (aHR 3.0, 95% CI 1.9–4.7 for intervals <6 mo; aHR 2.1, 95% CI 1.4–3.3 for intervals 6–8 mo; aHR 1.9, 95% CI 1.3–2.8 for intervals 9–11 mo; aHR 1.5, 95% CI 1.1–2.1 for intervals 12–23 mo; and aHR 2.4, 95% CI 1.5–3.7 for intervals ≥72 mo).
Developmental delay
 Thompson,35 2003 (United States)Cross-sectional (170 874 children)Developmental delay or disability in the first 3 y of life (including delayed cognition, physical/motor impairment, lack of communication skills, delayed social/emotional development, or lagging adaptive development)IPI; continuousMaternal age, education, and marital and socioeconomic status; infant's gender, birth weight, antenatal care; race/ethnicity; smoking; complications of labor/delivery; congenital anomalyShort intervals were associated with increased risk of developmental delay or disability in the first 3 y of life. The risk of developmental delay decreased significantly for each 1-mo increase in IPI since the birth of the previous sibling up to 60 mo (aOR for each 1-mo increase in IPI 0.995, 95% CI 0.993–0.997).
 Pilz,36 2007 (Brazil)Cross-sectional (197 children)Suspected developmental delay up to age 6 y (using the Denver II test for social contact, fine motor skills, language, and gross motor skills)BI; <19, ≥19aMaternal age and education, familial income, marital status, parity, pregnancy complications, birth weight, gestational age, neonatal and child morbidity, child care, breastfeeding, maternal supportIntervals <19 mo were associated with increased risk of suspected developmental delay (aOR 3.90, 95% CI 1.02–24.08).
 de Moura,37 2010 (Brazil)Cohort (3869 children)Suspected developmental delay at age 2 y (using the BSDI test for personal-social, adaptive, motor, communication and cognitive development)BI; <24, ≥24aMaternal age and education, race/ethnicity, antenatal care, child’s gender, socioeconomic status, smoking, pregnancy complications, infant's mode of delivery, gestational age, birth weight, 5-min Apgar score, child nutritional variables, breastfeeding duration, mother and child morbidity, child environmental stimuliIntervals <24 mo were associated with increased risk of suspected developmental delay (aRR 1.91, 95% CI 1.73–2.09).
Cerebral palsy
 Torfs,38 1990 (United States)Cohort (19 044 children)Cerebral palsy (diplegia, hemiplegia, quadriplegia, other spastic syndrome, athetosis, or cerebral palsy not otherwise specified that was not the result of a progressive disease or of a neural tube defect)IPI; <3, 3–36,a >36Race/ethnicity, parity, child’s gender, mother's work, pregnancy complications, length of menstrual cycle, birth weight, gestational age, birth defects, delivery characteristicsIntervals <3 mo or >36 mo were associated with a marginally significant increased risk of cerebral palsy (aRR 3.7, 95% CI 1.0–4.4).
 Pinto-Martin,39 1998 (United States)Cohort (375 infants weighing 500–2000 g at birth)Disabling cerebral palsy at a corrected age of 2 y (cerebral palsy plus any of the following conditions: inability to walk 5 steps unaided by age 2 y, receiving physical therapy for motor disability at the examination time, Bayley motor score >1 SD lower than performance score, surgical intervention for motor disorder, using braces or other physical assistance devices)IPI; <6, ≥6aBirth weight, gestational age, neonatal brain injury, maternal age, mother's education, amnionitisIntervals <6 mo were associated with increased risk of disabling cerebral palsy (aOR 2.7, 95% CI 1.1–7.1).
  • aHR, adjusted hazard ratio; aOR, adjusted odds ratio; aRR, adjusted relative risk; ASD, autism spectrum disorder; BI, birth interval; BSDI, Battelle Screening Developmental Inventory; DSM-IV-TR, Diagnostic and Statistical Manual, Fourth Edition, Text Revision; ICD-9, International Classification of Diseases, Ninth Revision; ICD-10, International Classification of Diseases, 10th Revision; IPI, interpregnancy interval; PDD-NOS, pervasive developmental disorder-not otherwise specified.

  • a Reference category.