Table 1.
Representative association studies between maternal diabetes and orofacial clefts
| Study Description | Subject Population and Years | Maternal Condition | OFC Number total included in study (prevalence); RR/OR (95% CI) | OFC Subtype total included in study (prevalence); RR/OR (95% CI) | Reference |
|---|---|---|---|---|---|
| Population-based study of association between PGDM and GDM and birth defects in mother-infant pairs from birth registry data | 29,211,974 live births with maternal age ranging from 18–49 years old documented in the National Vital Statistics System of USA, 2011–2018 | PGDM 242,600 mothers (0.83%) | 412 (0.170%); RR1 2.31 (2.10–2.55), P<0.0001 |
CL/P 273 (0.113%); RR 2.06 (1.82–2.33) P<0.001 CPO 139 (0.057%); RR 2.35 (1.97–2.97), P<0.001 |
Wu et al 2020 |
| GDM 1,685,479 mothers (6.18%) | 1,688 (0.100%); RR 1.36 (1.30–1.43), P<0.0001 |
CL/P 1,145 (0.068%); RR 1.28 (1.20–1.36), P<0.001 CPO 543 (0.032%); RR 1.40 (1.28–1.53) |
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| Analysis of association between PGDM and GDM and birth defects using case-control data from National Birth Defects Prevention Study (NBDPS) | 13,030 infants with and 4,895 without birth defects in USA, 1997–2003 |
PGDM
All birth defects group: 1.7% of mothers |
33 OFC cases |
CL/P Isolated 14; OR 2.92 (1.45–5.87) Syndromic 8; OR 8.07 (3.05–21.39) CPO Isolated 5; OR 1.8 (0.67–4.87) Syndromic 6; OR 10.73 (3.99–28.86) |
Correa et al 2008 |
|
GDM
All birth defects group: 4.7% of mothers |
96 OFC cases |
CL/P Isolated 54; OR 1.45 (1.03–2.04) Syndromic 8; OR 1.22 (0.52–2.86) CPO Isolated 29; OR 1.54 (1.01–2.37) Syndromic 5; OR 1.26 (0.50–3.20) |
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| Expanded analysis of NBDPS data | 31,007 infants with and 11,477 without birth defects in USA, 1997–2011 |
PGDM All birth defects group: 775 mothers (2.5%), Control group: 71 mothers (0.6%) |
58 CL/P cases; OR 3.0 (2.1–4.3) 42 CPO cases; OR 4.3 (2.9–6.5) |
CL/P Isolated 37; OR 2.2 (1.4–3.3) Syndromic 21; OR 8.7 (5.0–15.0) CPO Isolated 19; OR 2.5 (1.4–4.2) Syndromic 23; OR 12.3 (7.3–20.7) |
Tinker et al 2020 |
|
GDM All birth defects group: 1,653 mothers (5.3%), Control group: 536 mothers (4.7%) |
161 CL/P cases; OR 1.1 (0.9–1.3) 96 CPO cases; OR 1.4 (1.1–1.8) |
CL/P Isolated 143; OR 1.1 (0.9–1.4) Syndromic 18; OR 1.0 (0.6–1.7) CPO Isolated 79; OR 1.4 (1.1–1.8) Syndromic 17; OR 1.4 (0.9–2.4) |
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| Analysis of NBDPS data for association between PGDM and birth defects stratified by type 1 and type 2 DM | 29,024 infants with and 10,898 infants without birth defects in USA, 1997–20112 |
PGDM Type 1 All birth defects group: 252 mothers (0.9%); Control group: 24 mothers (0.2%) |
27 OFC cases |
CLP 10; OR 2.3 (1.1–4.7) CLO 23 CPO 15; OR 4.1 (2.1–7.8) |
Marchincin et al 2022 |
|
PGDM Type 2 All birth defects group: 357 mothers (1.2%); Control group: 34 mothers (0.3%) |
55 OFC cases |
CLP 23; OR 4.1 (2.3–7.1) CLO 13; OR 4.8 (2.4–9.3) CPO 19; OR 4.4 (2.4–7.8) |
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| Population-based study of association between PGDM and GDM and birth defects in mother-infant pairs from birth registry data | 650,914 singletons born in Upstate New York, 2004–2016 | PGDM: 4,134 mothers (0.6%) | 12 OFC cases (0.290%); OR 2.9 (1.6–5.2), P<0.001 |
CL/P 7 (0.169%); OR 2.5 (1.2–5.3), P<0.05 CPO 5 (0.121%); OR 3.8 (1.6–9.3), P<0.01 |
Yang et al 2019 |
| GDM: 32,605 mothers (5.0%) | 32 OFC cases (0.098%); OR 1.0 (0.7–1.4), P>0.05 |
CL/P 22 (0.067%); OR 1.0 (0.6–1.5), P>0.05 CPO 10 (0.031%); OR 1.0 (0.5–1.8), P>0.05 |
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| Population-based study of birth defects assessing PGDM attributable risk percentage | 2,839,680 live births in Canada (except Quebec), 2002–2013 |
PGDM Type 1
0.27% (2002) – 0.28% (2012) of mothers |
0.36% OFC prevalence; OR 2.48 (1.70–3.63) |
(No OFC subtype available) | Liu et al. 2015 |
| PGDM Type 2 0.19% (2002) – 0.47% (2012) of mothers | 0.39% OFC prevalence; OR 2.77 (2.02–3.80) |
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| Population-based study of association between PGDM and GDM and birth defects in mother-infant pairs from birth registry data | 1,216,198 births in Sweden, 1987–1997 | PGDM 3,864 mothers (0.32%) | 19 OFC cases (0.492%); OR 2.33 (1.49–3.67) |
(No OFC subtype available) Isolated 11 (0.285%) Syndromic 8 (0.207%) |
Aberg et al 2001 |
| GDM 8,688 mothers (0.72%) | 18 OFC cases (0.207%); OR 0.98 (0.62–1.56) |
Isolated 14 (0.161%) Syndromic 4 (0.046%) |
1
RR adjusted for maternal age, race/ethnicity, education levels, marital status, parity, smoking before and during pregnancy, timing of initiation of prenatal care, pregnancy BMI, infant sex, and pregestational hypertension.
2
Mothers were excluded if they had GDM, if their first DM diagnosis was during any pregnancy, if they had an unknown DM type or diagnosis date, or if they had a type 1 PGDM diagnosis but did not use insulin during pregnancy.
3
OR not calculated if n<3