**Background:** Congenital malformations are structural or functional alterations in fetal development that can result from genetic, environmental, or unknown causes. Maternal health status—including obesity, diabetes, and nutrition—is known to influence the intrauterine environment and risk of congenital anomalies. Maternal birth weight (MBW) has been linked to later-life noncommunicable diseases and pregnancy complications, but its association with congenital malformations in offspring has not been well studied, particularly in Asian populations. This study aimed to investigate the relationship between MBW and prevalence of congenital malformations in Japanese children using data from a large nationwide birth cohort.
**Methods:** This prospective study analyzed data from the Japan Environment and Children’s Study (JECS), which recruited 103,060 pregnancies from 15 Regional Centres across Japan between January 2011 and March 2014. After exclusions (multiple participation, multiple pregnancies, abortion/stillbirth, consent withdrawal, non-Japanese nationality, missing/improbable MBW data, missing questionnaires, chromosomal abnormalities, skeletal dysplasia, and sex mismatch), 78,366 mother-infant pairs were included. MBW was self-reported via the C6m questionnaire and categorized as <2500 g (low), 2500–2999 g, 3000–3499 g (reference), 3500–3999 g, or ≥4000 g (high). Data on infant congenital malformations were obtained from medical records at birth (Dr0m), one month (Dr1m), and two years (C2y questionnaire with physician transcription). Selected outcomes included: nervous system, eye/ear/face, cleft lip/palate, congenital heart disease, arrhythmia, urinary system (CAKUT, defined as hydronephrosis, cystic renal malformations, renal agenesis, bladder exstrophy/cloacal exstrophy), genital organs in male infants (with hypospadias and cryptorchidism as separate outcomes), limbs, angioma, and inguinal hernia. Covariates included maternal age, pre-pregnancy BMI, conception method, parity, history of mental illness, maternal congenital heart disease, uterine/urogenital malformations, kidney disease, smoking, alcohol consumption, marital status, education, income, drug use at <12 weeks gestation (including methimazole, SSRIs, other antidepressants, antianxiety, sleeping pills, antipsychotics, valproic acid, other antiepileptics, lithium), folic acid supplement use, HbA1c at <24 weeks, and infant sex. Binary logistic regression (with Firth correction for separation) was used, and multiple imputation (Markov chain Monte Carlo) was applied for missing covariates.
**Key Results:** Among the 78,366 participants, MBW distribution was: <2500 g (n=3850, 4.9%), 2500–2999 g (23,161, 29.5%), 3000–3499 g (38,146, 48.7%), 3500–3999 g (11,435, 14.6%), and ≥4000 g (1774, 2.3%). Mean maternal age was 30.9 years (SD 5.0) and pre-pregnancy BMI was 21.2 kg/m² (SD 3.2). Overall prevalence of key malformations: cleft lip/palate 0.21%, congenital heart disease 1.36%, CAKUT 0.35%, genital organs in male infants 1.12%, limbs 0.28%, angioma 0.77%, inguinal hernia 0.49%. After adjustment (Model 2), low MBW (<2500 g vs. 3000–3499 g) was significantly associated with increased odds of: congenital heart disease (aOR 1.388, 95% CI 1.075–1.792), genital organs in male infants (aOR 1.648, 95% CI 1.130–2.405), hypospadias (aOR 1.804, 95% CI 1.130–2.881), angioma (aOR 1.491, 95% CI 1.079–2.059), and inguinal hernia (aOR 1.746, 95% CI 1.189–2.565). High MBW (≥4000 g) was significantly associated with increased odds of arrhythmia (aOR 1.775, 95% CI 1.157–2.725) and CAKUT (aOR 2.194, 95% CI 1.261–3.819). In sex-stratified analyses: low MBW was linked to cleft lip/palate only in male infants (aOR 1.473, 95% CI 1.052–2.064), congenital heart disease in males (aOR 1.615, 95% CI 1.119–2.332), genital organs (aOR 1.648 for overall; hypospadias aOR 1.804), and inguinal hernia in males (aOR 1.484, 95% CI 1.189–1.851). High MBW was linked to congenital heart disease in males (aOR 1.745, 95% CI 1.058–2.877), arrhythmia in females (aOR 1.788, 95% CI 1.047–3.052), and CAKUT in males (aOR 2.470, 95% CI 1.350–4.517). Low MBW was also associated with CAKUT in females (aOR 1.619, 95% CI 1.154–2.273).
**Clinical Implications:** This is the first large-scale study to demonstrate an association between maternal birth weight and congenital malformations in a Japanese population. Low MBW (<2500 g) was linked to several malformations, including congenital heart disease, hypospadias, angioma, and inguinal hernia, while high MBW (≥4000 g) was associated with arrhythmia and CAKUT. Sex-specific patterns emerged, with stronger associations in male infants for some outcomes. These findings suggest that maternal birth weight may serve as a readily available clinical parameter to identify women at increased risk of having children with certain congenital anomalies. However, as the study is observational, causality cannot be inferred. The authors hypothesize that underlying mechanisms may involve epigenetic modifications, oxidative stress, or altered renin-angiotensin system activity related to maternal intrauterine environment. Clinicians should consider documenting maternal birth weight during first prenatal visits, but further research is needed to elucidate causal pathways and to validate findings across different ethnicities.