Low-normal birthweight in the first pregnancy as a risk factor for small for gestational age in the second pregnancy: A matched case-control study.

BACKGROUND

Recurrent obstetric complications may stem from chronic placental dysfunction or maternal vulnerability, with potential worsening across successive pregnancies. Subtle intrauterine growth restriction in a first pregnancy, even within the appropriate-for-gestational-age (AGA) range, may signal underlying risk for subsequent adverse outcomes.

OBJECTIVES

To determine whether low-normal birthweight in a first AGA pregnancy is associated with increased risk of small-for-gestational-age (SGA) birth in the second pregnancy among women with two consecutive term singleton births.

METHODS

We conducted a retrospective matched case-control study nested within a historical cohort of all births between 2014 and 2024. All cases (n = 125) that delivered a first AGA and a second SGA infant were included. Controls (n = 250) who delivered two consecutive AGA infants, matched 1:2 on infant sex and date of birth of the second child. Primary exposure was standardized birthweight Z-score of the first child, categorized as <-0.5 standard deviation (SD) or <-1 SD. Primary outcome was SGA birth (<10th percentile) in the second pregnancy. Logistic regression, adjusted for maternal age, prepregnancy weight, height, ethnicity, smoking, socioeconomic status, and time to conception, and generalized structural equation model (GSEM) accounted for within-woman correlation were performed.

RESULTS

Among 375 women analyzed, first-born infants of cases had lower mean birthweight than controls (3072 vs. 3375 g). Compared with reference birthweight (Z-score ≥-0.5 SD), first-born Z-score <-0.5 SD was associated with fivefold increased odds of subsequent SGA (adjusted odds ratio [aOR], 5.11; 95% confidence interval [CI], 2.51-10.41). Risk increased for Z-score <-1 SD (aOR, 8.52; 95% CI, 3.40-21.30), demonstrating dose-response (OR for trend 3.32; 95% CI, 2.16-5.10). GSEM confirmed findings (aOR, 5.46 and 8.00, respectively; ρ = 0.33). Quantitative bias analysis suggested that unmeasured confounding was unlikely to explain the observed associations.

CONCLUSIONS

Low-normal birthweight in a first AGA pregnancy is associated with subsequent SGA in the subsequent pregnancy suggesting an undetected placental or maternal vulnerability.