TABLE 3.
Summary of ID risk factors across studies.
| Risk factor | Studies | Odds ratio (or equivalent) | Summary |
| Socioeconomic status (Maternal SES Household disadvantage Local area deprivation) | Camp et al. (83) | For Black children, low SES RR 2.54. For White children, low SES RR 3.36. | Across studies, lower maternal socioeconomic status and relative area deprivation increased risk of ID in offspring. Majority of studies reported mild-moderate ID only; unknown if risk attributable to household disadvantage varies across ID level. |
| Drews et al. (75) | Low SES (mild ID): aOR 1.60 (1.00-2.50) (Mild ID, IQ 50–70). | ||
| Emerson (74) | Lower household SES: moderate ID (aOR = 2.34), severe ID (aOR = 2.42), pervasive multiple ID (aOR = 1.81). Area deprivation codes d1-d9 aORs significant for moderate ID (aOR 3.48 (3.38–3.57) at worst area) and severe ID (aOR 1.45 (1.36–1.55 at worst area). | ||
| Heikura et al. (69) | For any ID: 1966 cohort: SES IV Level 4 unskilled; aOR 1.70 (0.50–5.80). 1986 cohort: SES IV Level 4 unskilled, aOR 2.20 (1.20–3.90). For mild ID, being a farmer in 1966 cohort aOR 3.50 (1.10–11.40); and in 1986 cohort aOR 3.70 (1.40–9.80). For severe ID (IQ < 50), living in a remote area in 1966 cohort aOR 1.90 (1.00–3.60), level IV unskilled worker for 1986 cohort aOR 3.10 (1.40–6.70). | ||
| Leonard et al. (60) | Mothers from most socioeconomically disadvantaged area: mild-moderate ID OR 5.61 (2.50–3.91). | ||
| Leonard et al. (62) | Socio-economic disadvantage: mild-moderate ID, aOR 2.56 (2.27–2.97). | ||
| Louhiala (58) | Lowest social class at highest risk of any ID, aOR 1.70 (1.20–2.40). | ||
| Rantakallio (42) | Lower social class (farmers) higher risk: Social class I &II: mild ID 0.4 per 1000, moderate ID 0.4/1000. Social class IV: mild ID 2.5/1000, moderate ID 1.9/1000. | ||
| Stromme and Magnus (38) | Parents in Social Classes IV to V: increased risk of mild-moderate ID, OR 6.30 (0.70–23.50) for IV; OR 5.00 (1.50–15.60) for V. | ||
| Marital status | Leonard et al. (60) | Single mothers, mild-moderate ID OR 2.18 (1.97–2.42). | Children of single women at higher risk of mild-moderate ID. |
| Leonard et al. (62) | For mild-moderate ID, never married or single: OR 2.48 (2.30–2.67); widowed, divorced or separated: OR 2.60 (2.13–3.16). | ||
| Child sex | Croen et al. (13) | Male sex, mild ID aOR 1.90 (0.80–2.00). | Male children at higher risk of mild to severe ID; risk increases in children from minority ethnicity (Black children). |
| Drews et al. (75) | Male sex: aOR 1.60 (1.20–2.20) for mild ID (IQ 50–70), aOR 1.70 (1.10–2.50) for severe ID (IQ < 50). | ||
| Langridge et al. (64) | Male sex for mild ID, aOR 1.61 (1.50–1.73), and severe ID aOR 1.67 (1.24–2.24). | ||
| Leonard et al. (60) | Male sex, risk mild-moderate: OR 1.55 (1.43–1.68), severe: OR 1.83 (1.38–2.43), ASD OR = 3.97 (2.78–5.69). | ||
| Louhiala (58) | Male sex: any ID aOR 1.50 (1.10–2.10). | ||
| Oswald et al. (43) | Male American Indian: any ID (mild-severe) aOR 1.60; Male Black: aOR 4.03; Male Hispanic: any ID aOR 1.35; Female Black: any ID aOR 2.58 (type of ID unspecified). | ||
| Zheng et al. (30) | Male sex for mild ID aOR 1.23 (1.06–1.44); for severe ID aOR 1.14 (1.00–1.73). | ||
| Child birth order | Croen et al. (13) | Later born, mild ID aOR 1.30 (1.20–1.50). | Later born children consistently at higher risk of mild-moderate ID. |
| Drews et al. (75) | Children with two or more older siblings: aOR 1.60 (1.10–2.50) (Mild ID, IQ 50–70). | ||
| Leonard et al. (62) | Fourth or later born: mild-moderate ID, aOR 2.55 (2.27–2.87). | ||
| Leonard et al. (60) | Sixth or later born: mild-moderate ID, OR 3.13 (2.50–3.91). | ||
| Heikura et al. (69) | Multiparity (parity = 4) for 1966 cohort: any ID aOR 1.50 (0.60–3.60); 1986 cohort: any ID aOR 2.40 (1.20–4.90). For mild ID in 1986 cohort, parity = 4 aOR 2.40 (1.20–4.90). For severe ID in 1966 cohort, parity = 4 aOR 1.80 (1.00–3.40). | Multiparity increased odds for any ID; mild ID (later cohort) and severe ID (earlier cohort). | |
| Multiple births | Croen et al. (13) | Multiple births, mild ID aOR 1.20 (1.10–1.40). | Children of multiple births at higher risk of ID. |
| Louhiala (58) | Multiple births, risk of any ID aOR 5.60 (1.40–22.30). | ||
| Van Naarden et al. (35) | Proportions of multiple births in children with ID: Observed/expected 1.34 (0.95–1.73). | ||
| Parental employment and education (Maternal education Maternal employment Maternal income Paternal employment) | Camp et al. (83) | For Black children, low maternal education <9 years, any ID (IQ < 70) RR 2.34. For White children, low maternal education <9 years, ID (IQ < 70) RR 3.00. | Across studies, lower maternal education, typically less than 12 years, conferred highest risk of offspring having ID (mild to severe). |
| Chapman et al. (82) | Mothers with < 12 years education vs. some post-secondary education: any ID, RRR 7.00 (6.40–7.70); mild-moderate ID RRR 10.90 (9.60–12.30) and severe ID RRR 3.20 (2.60–3.80). Mothers with high school (education = 12 years): EMH RRR 3.80 (3.40–4.40), TMH 1.70 (1.40–2.00). | ||
| Decoufle and Boyle (79) | Lower maternal education and race-education interaction. Black mothers with <10 years education risk of ID (IQ < 70) aOR 2.90 (1.60–5.40); vs. for White mothers: aOR 9.10 (3.90–21.30). Maternal education (White and Black mothers combined) <8 years: aOR 6.10 (2.20–16.60) vs. >16 years education aOR 0.20 (0.10–0.50). | ||
| Decoufle et al. (78) | Children of blue-collar workers in textile products or apparel manufacturing industries, highest risk of ID (mild and severe combined): aOR 10.30 (1.30–81.70). | ||
| Drews et al. (75) | Maternal education <12 years: aOR 4.10 (2.40-6.90). Maternal education = 12 years aOR 1.80 (1.10-2.90) (Mild ID, IQ 50–70). | ||
| Leonard et al. (60) | Higher risk for fathers not in the workforce: Mild-moderate ID, OR 5.84 (4.61–7.40), severe ID 3.88 (1.87–8.10). | ||
| Zheng et al. (30) | Mother illiterate compared to senior high school or above, for mild ID aOR 1.74 (1.21–2.52), for severe ID aOR 2.45 (1.65–3.63). | ||
| Young maternal age | Chapman et al. (82) | Maternal age 15–19 any ID RRR 2.40 (2.30–2.60), for EMH (mild), age 15–19 RRR 2.70 (2.50–3.00). | Children of younger mothers (<20 years) have an increased risk of mild-moderate ID |
| Leonard et al. (60) | Maternal age <20 years, mild-moderate ID OR 2.09 (1.82–2.40). | ||
| Leonard et al. (62) | Maternal age <20 years, mild-moderate ID aOR 1.88 (1.57–2.25). | ||
| Advanced maternal age | Chapman et al. (82) | Maternal age >35 years: any ID, highest RRR maternal age 40-44 = 2.20 (1.60–2.80). For TMH only (IQ 25–54) maternal age 35–39 RRR 2.40 (1.60–3.60) and age >40 RRR 3.50 (1.90–6.50). | Older mothers (>35 years), risk of mild to severe ID. |
| Croen et al. (13) | Maternal age >35 years, mild ID aOR 1.40 (1.20–1.60). | ||
| Drews et al. (75) | Maternal age >30: severe ID aOR 1.80 (1.10-3.10). Maternal age >30 years: any ID with other neurological condition aOR 2.00 (1.20–3.30). | ||
| Williams and Decoufle (33) | Black race mothers aged 30–34, aOR 3.04 (1.02–9.02) and aged over 35, aOR 3.88 (0.91–16.64). | ||
| Zheng et al. (30) | Maternal age >34 mild ID aOR 1.47 (1.15–1.88) Maternal age>34: severe ID aOR 1.32 (1.14–2.05). | ||
| Paternal age | Leonard et al. (62) | Paternal age > 39 years, mild-moderate ID aOR 1.59 (1.36–1.86). | Limited evidence to suggest an increased risk. For older fathers. |
| Parental intellectual disability | Zheng et al. (30) | Mild ID aOR 8.81 (6.45–12.06), severe ID aOR 7.10 (5.09–9.91). | Children of parents with ID at increased risk of ID. |
| Maternal ethnicity/Race | Abdullahi (29) | Indigenous mothers: ID (IQ < 70), aRRR 1.75 (1.60–1.92); CP with ID, aRRR 1.74 (1.25–2.41). Foreign-born low-income mothers: ASD with ID, aRRR 2.34 (0.96–5.70). Upper-middle-income countries: ASD with ID, aRRR, 1.12 (0.70–1.78). | Indigenous and Black mothers consistently confer higher risk to offspring having ID. Insufficient evidence for other ethnicities. Mothers from minority ethnicity generally confer higher risk to offspring. |
| Croen et al. (13) | Black race, mild ID (IQ 50–70) aOR 1.50 (1.40–1.70). Asian, mild ID aOR 0.70 (0.60–0.80) (protective). Hispanic, severe ID aOR 1.20 (1.00–1.40). Asian, severe ID 1.30 (1.00–1.70). | ||
| Drews et al. (75) | Black race: mild ID (IQ 50–70) aOR 1.80 (1.30–2.60). | ||
| Emerson (74) | Gypsy/Romany ethnicity: MLD (moderate ID) aOR 2.84 (2.64–3.05). Traveller of Irish Heritage: SLD (severe ID) aOR 1.90 (1.38–2.61), MLD aOR 3.52 (3.20–3.88). Pakistani ethnicity: PMLD (pervasive multiple ID) aOR 2.33 (2.08–2.61). | ||
| Leonard et al. (60) | Indigenous: mild-moderate ID OR 2.83 (2.52–3.18). | ||
| Leonard et al. (62) | Indigenous: mild-moderate ID aOR 1.60 (1.41–1.82). | ||
| Oswald et al. (43) | Any ID by Gender/Ethnicity: Male American Indian, aOR 1.60; Male Black, aOR 4.03; Male Hispanic, aOR 1.35; Female Black, aOR 2.58. | ||
| Williams and Decoufle (33) | Black race for mothers aged 30–34, co-developmental ID (CNS birth defect, with or without another developmental disability) OR 1.91 (0.89–4.09) and aged >35, OR 4.01 (1.45–11.09). | ||
| Yeargin-Allsopp et al. (32) | Black race: mild ID, aOR 1.80 (1.30–2.60). | ||
| Preterm birth | Bilder et al. (85) | Gestational age <37 weeks: mild and severe ID combined for inclusive group (all ID), aOR 3.07 (1.98–4.76); combined ID for exclusive group (only those without a known genetic cause of ID), aOR 3.58 (2.15–5.95). | Preterm birth <37 weeks increased risk of ID; preterm birth with low birthweight <2,500 g conferred greatest risk. |
| Langridge et al. (64) | Medically induced PTB with mild-moderate ID: aOR 1.25 (1.04–1.49). | ||
| Luu et al. (57) | FSIQ adj. mean diff for all children preterm vs. term: -13.70 (-17.10, -10.30) (p < 0.005). FSIQ adj. mean diff preterm vs. term excluding brain injury children: -11.70 (-14.70, -8.70) (p < 0.005). | ||
| Mervis et al. (47) | <2,500 g preterm mild ID aOR 1.90 (0.90–4.30), severe ID aOR 2.60 (1.00–7.10); >2,500 g preterm mild ID 2.20 (1.30–3.90). | ||
| Schieve et al. (40) | ID (IQ < 70) without ASD: PTB (<37 weeks) aRR 2.10 (1.90–2.20). VPTB (<32 weeks) aRR 5.40 (4.80–5.90). | ||
| Heuvelman et al. (68) | 24 weeks GA, aOR 14.54 (11.46–18.44]; at 32 weeks, aOR 3.59 (3.22–4.01]; at 37 weeks, aOR 1.50 (1.38–1.63); at 39 weeks, aOR 1.10 (1.04–1.17); at 42 weeks, aOR 1.16 (1.08–1.25); at 44 weeks, aOR 1.71 (1.34–2.18) (67). | ||
| Low birthweight | Bilder et al. (85) | LBW <2,500 g: mild and severe ID, aOR 4.07 (2.34–7.09). | LBW <2,500 g consistently increased risk of mild ID, and in one study severe ID. |
| Croen et al. (13) | LBW, mild ID aOR 4.30 (4.00–4.60). | ||
| McDermott et al. (50) | All mild ID: LBW (<2,500 g) at age 5 years: all aOR 3.40 (2.10–5.40); Black aOR 2.70 (1.40–5.40); non-Black aOR 3.90 (2.00–7.50). LBW (<2,500 g) at age 9–11 years: all aOR 1.20 (0.70–2.00); Black aOR 4.10 (1.40–12.00); non-Black aOR 0.80 (0.40–1.60). | ||
| Mervis et al. (47) | At any term birth: Risk of mild ID: LBW <2,500 g aOR 2.40 (1.60–3.80), VLBW <1,500 g aOR 11.70 (2.50–54.70). Risk of severe ID: <2,500 g aOR 4.40 (2.60–7.50), <1,500 g aOR 29.40 (5.80–148.20). Fullterm birth: <2,500 g mild ID aOR 2.20 (1.20–4.00), severe ID aOR 3.70 (1.70–7.90). | ||
| Schieve et al. (40) | ID (IQ<70) LBW (<2,500 g) aRR 3.20 (3.00–3.40); VLBW (<1,500 g) aRR 7.80 (7.00–8.70); Term LBW aRR 2.40 (2.10–2.70). | ||
| Birth weight for gestational age, SGA, birthweight percentiles. Gestational age Intrauterine growth (% optimal birth weight), severe growth restriction | Bilder et al. (85) | SGA: mild and severe ID, aOR 3.43 (2.21–5.33). | SGA conferred greater risk of ID in offspring across studies. Risk of ID was greatest in those born extremely early, lessening with advancing GA but increasing post term. Inappropriate intrauterine growth, less than or greater than optimal birth weight, are associated with development of ID. |
| Chen et al. (80) | LBW percentile groups vs. reference group (40th–59th percentiles): 10th–24th percentiles aHR 1.43 (1.22–1.67) and 25th–39th percentiles: aHR 1.28 (1.10–1.50) in population analysis; aHR 1.52 (1.00–2.31) and aHR 1.44 (1.00–2.09) in sibling comparison analysis. | ||
| Louhiala (58) | SGA: aOR 4.40 (2.10–9.30). | ||
| Schieve et al. (40) | ID (IQ<70) SGA aRR 1.90 (1.80–2.00); VSGA aRR 2.30 (2.10–2.50); term SGA aRR 1.60 (1.50–1.70). | ||
| Langridge et al. (64) | POBW of <75%: mild ID aOR 2.33 (1.97–2.75) and severe ID aOR 3.77 (2.15–6.61). | ||
| Leonard et al. (61) | IUGR in Caucasian children: mild–moderate ID for preterm births (<37 weeks) aOR 1.71 (1.06, 2.77), term births (>37 weeks) aOR = 2.42 (1.88, 3.12). Severe ID aOR 4.79 (2.59, 8.83) for term births. SGR overall, severe ID: aOR 3.20 (1.30– 7.90). Excess intrauterine growth: autism with ID, aOR 2.36 (0.93–6.03). | ||
| Maternal smoking during pregnancy | Drews et al. (76) | Smoking overall: aOR 1.44 (0.92–2.27); during 2nd trimester: aOR 1.53 (0.80–2.46). | Smoking during pregnancy increased risk of ID; risk may be greater in later trimesters. |
| Maternal body weight or diabetes | Heikura et al. (69) | Pre-pregnancy maternal obesity in second cohort, year 1986 any ID risk aOR 2.80 (1.50–5.30). For mild ID in 1986 cohort, BMI>30 aOR 2.90 (1.30–6.10). | Pre-pregnancy or during pregnancy maternal obesity, and maternal diabetes of any stage conferred higher risk of ID in offspring. Gestational weight gain or loss not associated with greater risk. |
| Langridge et al. (64) | Maternal diabetes: mild-moderate ID, aOR 1.27 (1.00–1.61). | ||
| Leonard et al. (63) | Maternal diabetes: mild-moderate ID, aOR 1.38 (0.99–1.91, p = 0.06); autism with ID, aOR 2.95 (1.30–6.73). | ||
| Li et al. (59) | ID only (no ASD): Obesity: aHR 1.64 (1.09–2.45), pre-gestational diabetes (PGDM): aHR 2.26 (1.25– 4.09), obesity with PGDM: aHR 3.63 (1.73–7.61), and obesity with gestational diabetes (GDM): aHR 2.31 (1.00–5.36). AD+ID: obese GDM, aHR 6.53 (2.45–17.38), obese PGDM 9.73 (4.07–23.27). | ||
| Mann et al. (54) | Risk of any ID (IQ range not refined): Pre-pregnancy morbid obesity, aOR 1.52 (1.30–1.77). Risk of severe ID: Pre-pregnancy morbid obesity, aOR 1.83 (1.31–2.56). | ||
| Mann et al. (53) | Risk of any ID (IQ ranged not defined): Any diabetes, aOR 1.09 (1.01–1.19); chronic diabetes, aOR 1.31 (0.83–2.06), GDM, aOR 1.08 (0.98–1.19); diabetes of uncertain timing, aOR 1.12 (0.95–1.31). | ||
| Maternal PET or eclampsia, maternal hypertension | Griffith et al. (71) | Mothers with preeclampsia (PET), risk of any ID (IQ range not defined) aOR 1.38 (1.16–1.64), mothers with PET including child with LBW, aOR 1.28 (1.07–1.52). | Maternal PET or hypertension conferred higher risk of ID in offspring, irrespective of LBW. |
| Langridge et al. (64) | Pregnancy hypertension: mild-moderate ID, aOR 1.39 (1.25–1.54). | ||
| Salonen and Heinonen (41) | Pregnancy hypertension: risk of any ID (IQ range not defined) aRR 6.10 (1.30–28.90). | ||
| Paternal epilepsy | Tomson et al. (36) | Fathers with epilepsy, risk of any ID aHR 1.80 (1.20–2.90) vs. without epilepsy. Fathers with epilepsy and antiepileptic drugs (AED) only during conception, risk of any ID aHR 1.15 (0.49–2.70) vs. non AED. Fathers with epilepsy exposed to AED, risk of ID aHR 1.20 (0.60–2.60) vs. fathers with epilepsy unexposed to AED. Fathers with epilepsy exposed to valproic acid (VPA), risk of ID aHR 1.60 (0.50–5.10), vs. no AED. | No evidence for an association between paternal exposure to AEDs and risk of ID. But risk of ID increased in children of fathers with epilepsy, not related to AED medication. |
| Maternal epilepsy | Leonard et al. (63) | Maternal epilepsy: mild-moderate ID, aOR 3.01 (2.10–4.33), and autism with ID, aOR 5.80 (2.14–15.74) | Maternal epilepsy and the anti-epileptic drug valproic acid conferred higher risk of ID in offspring. |
| Blotiere et al. (84) | AED VPA: increased risk for isolated ID aHR 3.10 (1.50–6.20) vs. lamotrigine. Dose-response relationship with VPA; the highest HR of ID was for the highest mean daily dose [=1,500 mg: HR = 7.30 (3.00–17.70)]. Women treated for epilepsy (n < 100) AED VPA: risk of any ID aHR 4.00 (1.90–8.60) vs. lamotrigine. | ||
| Tomson et al. (36) | Mothers with epilepsy, risk of any ID aHR 2.40 (1.80–3.10) vs. mothers without epilepsy. Mothers with epilepsy and AED exposure, risk of any ID aHR 4.80 (2.10–10.80) vs. unexposed to AED. Mothers with epilepsy who used AED during pregnancy, risk of ID for VPA aHR 9.60 (3.50–26.20), for carbamazepine aHR 4.70 (1.80–12.50), for “other” AED aHR 4.70 (1.40–16.40), for lamotrigine aHR 2.50 (0.90–7.20), vs. unexposed to any AED. | ||
| Maternal asthma | Langridge et al. (64) | Mild-moderate ID: aOR 1.28 (1.12–1.47). | Maternal asthma conferred risk of mild-moderate ID in offspring. |
| Leonard et al. (63) | Mild-moderate ID: aOR 1.25 (1.02–1.54). | ||
| Maternal trichomoniasis | Mann et al. (55) | Risk of any ID: aHR 1.28 (1.12–1.46); severe ID: aHR 1.84 (1.35–2.51). | Maternal trichomoniasis associated with slightly increased risk of any ID. |
| Maternal UTI | Langridge et al. (64) | Mild-moderate ID with urinary tract infection (UTI), aOR 1.36 (1.19–1.55). | Across studies, increased risk of ID with UTI during pregnancy. Risk of ID following UTI in pregnancy may be dependent on antibiotic treatment, and confer a higher risk during the third trimester. |
| Leonard et al. (63) | Maternal renal or urinary condition: mild-moderate ID, aOR 1.65 (1.06–2.56). | ||
| McDermott et al. (51) | Unfilled script vs. no UTI controls, any ID or developmental delay, aRR 1.31 (1.12–1.54). Unfilled script vs. filled script for UTI, any ID or developmental delay aRR 1.22 (1.02–1.47). | ||
| McDermott et al. (49) | UTI during pregnancy, ID (IQ < 70) aRR 1.16 (1.00–1.29); UTI during Trimester 3, ID (IQ < 70) aRR 1.40 (1.01–1.95). | ||
| Anaemia | Camp et al. (83) | Among Black women, lowest recorded hematocrit <32 mg % among Blacks, ID (IQ < 70) RR 1.35. | Maternal or infant anaemia associated with higher risk of ID in offspring; this may be mediated by gestational age. |
| Hurtado et al. (67) | Anaemia increased risk of mild-moderate ID: aOR 1.28 (1.05–1.60). | ||
| Leonard et al. (63) | Maternal anaemia: severe ID, aOR 4.93 (2.00–12.09). | ||
| Maternal inflammation (Mid-gestational maternal cytokine and chemokine levels. Placental inflammation) | Chen et al. (81) | Placental inflammation: IQ <70 at 7 years old, aOR 1.20 (0.97–1.48), IQ 70–79, aOR 1.03 (0.89–1.18); indirect effects of shorter gestational age. | Maternal inflammation during pregnancy associated with greater risk of mild ID, which may be mediated by gestational age. Maternal serum cytokines IL-8 and MCP-1 may have a protective effect, whereas GM-CSF, IL-1α, IL-6, and IFN-γ were associated with an increased risk of ASD with ID. |
| Jones et al. (65) | ID v general population, reduced risk: IL-1B, aOR 0.91 (0.83–1.00); IL-8, aOR 0.81 (0.70–0.93); MCP, aOR 1: 0.76 (0.59–0.98). | ||
| Maternal mental illness | Di Prinzio et al. (77) | Any severe maternal mental illness increased risk of genetic or unknown cause ID, aOR: 1.70 (1.50–1.90). Schizophrenia, aOR 1.70 (1.30–2.30). | Any maternal psychiatric disorder or mental health condition increased risk of ID in offspring; including ASD with ID. Across 4 studies, affective disorders, schizophrenia and any mental illness consistently increased risk. |
| Fairthorne et al. (72) | Any previous psychiatric contact: ID of unknown cause aOR 2.14 (1.90–2.40), ID of known cause (not Down syndrome) aOR 2.13 (1.60–2.80), ASD with ID aOR 1.77 (1.30–2.40). Substance abuse disorders: ASD/ID aOR 2.26 (1.10–4.80). Schizophrenia: any ASD or ID aOR 2.66 (1.60–4.40) any ID aOR 2.53 (1.40–4.50); ID of unknown cause aOR 2.20 (1.10–4.40). Affective disorders: ASD with ID aOR 2.23 (1.50–3.20); ID of unknown cause aOR 1.89 (1.60–2.20); ID of known cause (not Down syndrome) aOR 1.71 (1.10–2.70). | ||
| Morgan et al. (46) | For any ID (including borderline ID of IQ 70–74, including “rare disorders”): Bipolar disorder, aOR 2.60 (1.50–4.40). Unipolar depression, aOR 2.70 (1.60–4.50). | ||
| Wang et al. (34) | For any ID of unknown cause: Bipolar disorder: males aOR 1.95 (1.53–2.48), females aOR 1.63 (1.20–2.22). Unipolar depression: males aOR 1.34 (1.14–1.59), females aOR 1.59 (1.30–1.95). | ||
| Maternal alcohol use | O’Leary et al. (45) | All for any ID (mild-moderate to severe): Non-Aboriginal: Any alcohol diagnosis: aOR 1.44 (1.18–1.75). During pregnancy: aOR 2.89 (1.62–5.18). Aboriginal: Any alcohol diagnosis: aOR 1.66 (1.42–1.96). During pregnancy: aOR 3.12 (2.13–4.56). | Maternal alcohol consumption increased risk of ID. |
| Environmental (Geographical remoteness Air pollutants Seasonality Soil concentration) | Emerson et al. (73) | Across 6 age waves (9 months, 3, 5, 7, 11, 14 years), risk of living in areas with top 20% rates of air pollutants: any ID (as defined in study, see Tables 1, 2) exposure RRs = 1.23 (1.00–1.49) for diesel particulate matter, 1.24 (1.02–1.50) for nitrogen dioxide, 1.31 (1.10–1.56) for carbon monoxide and 1.38 (1.11–1.70) for sulphur dioxide. | Environmental factors, including air pollutants, seasonality (month of conception), mineral concentrations in soil during pregnancy, and geographical remoteness all increased risk of ID in offspring. |
| Mackay et al. (56) | For any ID (IQ range not defined, qualifying for “Special Education”): First quarter conception (January–March) aOR 1.23 (1.18–1.29), quarter 2 aOR 1.17 (1.12–1.22), quarter 4 aOR 1.13 (1.09–1.18). | ||
| McDermott et al. (48) | Increased risk of any ID of unknown cause (mild to severe grouped): for I unit in change in arsenic soil concentration: aOR 1.13 (1.05–1.22); for 1 unit change in lead oil concentration: aOR 1.002 (1.000–1.004). | ||
| McDermott et al. (52) | Mercury, arsenic, barium, lead increased risk of any ID of unknown cause. Mild ID: te(Hg) est df = 2.224, chi-square = 11.176, p = 0.007. Severe ID: te(As, Pb) (interaction term) est df = 7.018, chi square = 12.996, p = 0.037. Any ID: te(As,Pb) (interaction term) est df = 1.368, chi square = 6.073, p = 0.006; te(Hg) est df = 1.641, chi square = 9.964, p = 0.006. | ||
| Onicescu et al. (44) | Mild ID (and/or placement in a public school for educable or mild MR), moderate/severe ID (and/or placement in a public school for trainable (moderate) or profound ID), and unspecified ID, all without known cause. Increased risk overall ID (all severities): Arsenic: β1 = 0.013 (0.00074, 0.038). Mercury: β1 = 0.11 (0.021, 0.39). | ||
| Zheng et al. (30) | Higher risk for rural areas compared to urban, for mild ID aOR 1.93 (1.55–2.41), for severe ID aOR 1.35 (1.09–1.67). |
There is variability in reporting ID severity. Categories of ID severity are classified according to the International Classification of Diseases, Ninth Revision (ICD-9) as mild (IQ = 50–70), severe (IQ < 50), or unspecified (13). Cases classified using DSM IV recommendations (American Psychiatric Association, 1994) follow “mild” (IQ 50–55 to 69); “moderate” (IQ 35–40 to 40–54); and “severe (including profound)” (IQ < 35 or 40) (59). If a classification is not listed, the study did not specify the level of ID, the IQ range, or used different terminology. ID, intellectual disability; RRR, relative risk ratio; CP, cerebral palsy; ASD, autism spectrum disorder; EMH, educable mentally handicapped (mild ID); TMH, trainable mentally handicapped(moderate to severe ID); OR, odds ratio; RR, risk ratio; SES, socioeconomic status; PTB, preterm birth; VPTB, very preterm birth; LBW, low birth weight; VLBW, very low birth weight; SGA, small for gestational age; VSGA, very small for gestational age; HR, hazard ratio; POBW, proportion of optimal birth weight; IUGR, intrauterine growth retardation; BMI, body mass index; PGDM, pre-gestational diabetes; GDN, gestational diabetes; PET, preeclampsia; AED, antiepileptic drugs; VPA, valproic acid; UTI, urinary tract infection.