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. 2021 Jun 23;9:675775. doi: 10.3389/fped.2021.675775

Table 1.4.

LGA and high birth weight and long-term outcomes—type 1 and type 2 diabetes.

Author, year, country Study design Cases Outcomes (risk estimates) Reference group (weight) Comments/adjustments Risk of bias Directness Precision
Type 1 and type 2 diabetesSystematic review/meta-analysis n = 6
Cardwell et al. (2010), UK (137) • Type 1 diabetes
• Meta-analysis
• Cohort n = 5 case–control n = 20
• 30 populations
12,087 • Birth weight >4,000 g:
• OR (cohort studies) 1.15 (95% CI 1.05–1.26)
• OR (case–control studies) 1.05 (95% CI 0.95–1.17)
• AOR (all studies) 1.11 (95% CI 1.03–1.20)
3,000–3,500 g All ages included in risk estimates not only children/adolescents <18 years
Harder et al. (2007), Germany (158) • Type 2 diabetes
• Meta-analysis
• cohort n = 10
• case–control n = 3
6,901 • Birth weight >4,000 g:
1OR 1.27 (95% CI 1.01–1.59)
2OR 1.36 (95% CI 1.07–1.73)
1 ≤ 4,000 g
22,500 g
• 4,000 g
No separate OR calculated for children/adolescents <18 years
Harder et al. (2009), Germany (18) • Type 1 diabetes
• Meta-analysis
• cohort n = 2
• case–control n = 10
7,491 • Birth weight >4,000 g:
• OR. 1.17 (95% CI 1.09–1.26)
• AOR 1.43 (95% CI 1.11–1.85)
<4,000 g Adjusted for confounders in seven of the included studies and wide difference in the number of confounders ranging from 2 to 14
Knop et al. (2018), China (160) • Type 2 diabetes
• Systematic review, meta-analysis
• 49 studies
• Cohort n = 36
• Case–control n = 8
• Cross-sectional n = 5
• (for high birth weight 32 studies)
43,549 • Birth weight >4,500 g:
• OR 1.19 (95% CI 1.04–1.36)
4,000–4,500 g Adult only (>18 years)
Whincup et al. (2008), UK (159) Type 2 diabetes systematic review, meta-analysis 6,260 • Per 1,000-g increase:
• OR 0.80 (95% CI 0.72–0.89)
• Birth weight >4,000 g:
• OR 1.35 (95% CI 0.67–2.72)
<4,000 g Adults
Zhao et al. (2018), China (161) • Type 2 diabetes
• Meta-analysis,
• Cohort n = 16
• Case–control n = 5
22,341 • Birth weight >4,000 g:
• OR was calculated for all ages:
• OR 1.11 (95% CI 1.00–1.24)
2,500–4,000 g Only 2 studies were limited to children/adolescents less than 18 years, both were case–control studies. No separate calculated OR for children/adolescents separately
Original articles
Type 1 diabetesOriginal articles n =20
Bock et al. (1994), Denmark (144) Case–control 837 • No statistical differences in mean birth weight between the cases and controls:
• 3,381, SD 536 g vs. 3,351, SD 602 g
• Exclusion criteria: mother with IDDM at the time of birth
• No risk estimates
Serious Good Fair
Borras et al. (2011), Spain (145) Case–control 306 • LGA >90 percentile
• OR for diabetes 1.45 (95% CI 1.02–2.07)
10–90th percentile • No adjustment
• 43 of originally 349 cases excluded due to missing data on birth weight
Serious Good Fair
Cardwell et al. (2005), UK (138) Cohort study 991 • Birth weight >4,000 g:
• ARR 1.68 (95% CI 1.30–2.18)
• Birth weight 3,500–3,999 g:
• ARR 1.48 (95% CI 1.20–1.83)
<3,000 g • Adjusted for maternal age, birth order, year of birth, gestational age
• Missing data 8%
Moderate Good Good
Goldacre (2017), UK (139) Cohort study 2,969 • Birth weight 4,000–5,499 g:
• AHR 1.12 (95% CI 0.99–1.27)
• Birth weight 3,500–3,999 g:
• AHR 1.11 (95% CI 1.02–1.22)
3,000–3,499 g Adjusted for infant sex, gestational age, maternal type 1 diabetes, maternal obesity, deprivation quintile, and caesarean section Moderate Good Good
Haynes et al. (2007), Australia (146) Cohort 840 • Birth weight ≥4,000 g:
• IRR 1.19 (95% CI 0.95–1.49)
• Birth weight 3,500–3,999 g:
• IRR 1.09 (95% CI 0.92–1.28)
3,000–3,499 g Adjusted for maternal age, gestational age, birth order, and year of birth Moderate Good Good
Levins et al. (2007), UK (140) Cohort 518 • Estimated rate of diabetes (<15 years) in birth weight categories:
• 3,500–3,999: Rate 1.55 (95% CI 1.28–1.86)
• ≥4,000: Rate 1.65 (95% CI 1.17–2.26)
No ref group Adjusted for year of birth, Rates only per 1,000 individuals presented. No difference between birth categories Serious Good Fair
Jones et al. (1999), UK (147) Case–control study 315 • Birth weight 3,500–3,900 g:
• ARR 1.00 (95% CI 0.74–1.36)
• Birth weight ≥4,000 g:
• ARR 1.15 (95% CI 0.76–1.75)
3,000–3,499 g Adjusted for maternal age, parity, birth weight for gestational age, gestational age and year of birth. Data included in Ievins (1997) and more restricted data material Moderate Good Fair
Khashan et al. (2015), Sweden (141) Cohort study 13,944 • Birth weight 4,000–5,500 g:
• ARR 1.01 (95% CI 0.96–1.05)
• LGA (+2 SD above mean) vs. AGA
• RR 1.14 (95% CI 1.04–1.24)
3,000–3,999 g Adjusted for offspring age as a time-dependent variable, year of birth, maternal age, education, BMI, country of origin, pre-gestational diabetes, gestational diabetes and infant sex Low Good Good
Kuchlbauer et al. (2014), Germany (142) Cohort study 1,117 No risk estimate available. cases with type 1 diabetes had higher birth weight measured as SDS (0.15 vs. 0.03) than the newborn in the control SDS (z-scores) are calculated from birth weights based on population reference values No adjustment. No risk estimates Critical Good Fair
Lawler-Heavner et al. (1994), USA (148) Case–control study 221 • Birth weight 3,500–3,999 g:
• AOR 0.9 (95% CI 0.5–1.7)
• Birth weight ≥4,000 g:
• AOR 1.0 (95% CI 0.4–2.5)
<3,000 g Adjusted for sex, age and birth in Colorado Serious Good Fair
McKinney et al. (1999), UK (149) Case–control study 196 • Birth weight ≥3,500 g:
• OR 1.01 (95% CI 0.68–1.51)
2,500–3,000 g Uncertain whether the results are adjusted or not Serious Good Fair
Metcalfe and Baum (1992), UK (150) Case–control study 952 • Results given according to proportions in three categories of birth weight:
• <2,500: insulin-dependent diabetes mellitus (IDDM) 65 (7%), Office of Population Censuses and Surveys (OPCS) 32,779 (6%)
• 2,500–3,999: IDDM 783(82%), OPCS 509707 (86%)
• ≥4,000: IDDM 104 (11%), OPCS 46012 (8%)
No adjustments. No risk estimates. No conclusions drawn Serious Good Fair
Patterson et al. (1994), UK (151) Case–control study 529 • Birth weight ≥4,000 g;
• OR 1.14 (95% CI 0.75–1.74)
2,500–3,999 g No adjustments Serious Good Fair
Rosenbauer et al. (2008), Germany (152) • Case–control
• Nationwide hospital-based surveillance (ESPED)
• 760
• 719 cases in birthweight analysis
• Birth weight ≥4,000 g:
• AOR 1.28 (95% CI 0.94–1.73)
3,000–3,999 g Probably adjusted for familiar type 1 diabetes, social status, maternal age, number of siblings and change of residency Moderate Good Fair
Stene et al. (2001), Norway (143) Cohort study 1,824 • 3,500–3,999 g: RR 2.11 (95% CI 1.24–3.58)
• 4,000–4,499 g: RR 2.38 (95% CI 1.39–4,06)
• ≥4,500 g: RR 2.21 (95% CI 1.24–3.94)
<2,000 g Adjusted for sex, maternal age, plurality, birth weight, gestational age, caesarean section, pre-eclampsia, year of birth Low Good Fair
Stene and Joner (2004), Norway (153) Case–control study 545 • 3,500–3,999 g: AOR 0.94 (95% CI 0.44–1.99)
• ≥4,000 g: AOR 1.01 (95% CI 0.46–2.29)
<2,500 g Adjusted for sex, maternal age, plurality, birth weight, gestational age, caesarean section, pre-eclampsia, duration of breast feeding, maternal education, atopic eczema, allergic rhino-conjunctivitis and asthma Low Good Fair
Tai et al. (1998), Taiwan (154) Case–control 117 • Birth weight ≥4,000 g:
• AOR 0.97 (95% CI 0.39–2.45)
<3,000 g Adjusted for age, sex Critical Poor Poor
Wadsworth et al. (1997), UK (155) Case–control • 281
• 218 cases included in the analysis
• No significant association with birth weight analyzed as a continuous variable
• Unadjusted OR per kg increase in birth weight 0.94 (95% CI 0.65–1.35)
Unadjusted Serious Good Poor
Waernbaum et al. (2019), Sweden (156) Case–control study 14,949 AOR 1.08 (95% CI 1.06–1.10) Birth weight z-score category with the interval 0–1 as reference Adjusted for urinary tract infection, PROM, maternal age, PTB, maternal BMI Low Good Good
Wei et al. (2006), Taiwan (157) Case–control study 277 ≥4,000 g: AOR 1.01 (95% CI 0.46–2.29) <2,600 g Adjusted for age, sex, socioeconomy, family history of diabetes„ delivery order, breast feeding, BMI, and GDM Moderate Fair Fair
Type 2 diabetes
Hu et al. (2020), China (163) Cohort 48,118 ≥4,000 g: AOR 1.20 (95% CI 1.07–1.34) 2,500–3,499 g Adjustments: age, gender, smoking, drinking, education, physical activity, diet habits, systolic blood pressure, dyslipidemia, BMI Moderate Fair Good
Zhu et al. (2013), China (164) Cross-sectional survey • 903 children with overweight
• 2 with type 2 diabetes
• 6 with impaired fasting glucose
• 16 with impaired glucose tolerance
• 2 with impaired fasting glucose + impaired glucose intolerance
• Birth weight ≥4,000 g:
• AOR 1.92 (95% CI 1.06–3.49)
• Subgroup of girls analyzed separately:
• AOR 4.38 (95% CI 1.21–15.85)
2,500–3,999 g Adjusted for age, gender, parental education. Only few children with type 2 diabetes or impaired fasting glucose Moderate Fair Fair

LGA, large-for-gestational-age; AGA, appropriate-for-gestational-age; HOMA-IR, homeostasis model assessment-insulin resistance; MS, metabolic syndrome; GDM, gestational diabetes mellitus; LBW, low birth weight; HBW, high birth weight; NBW, normal birth weight.