Threshold Effects of Third‐Trimester Maternal Vitamin A on Neonatal Ponderal Index: A Segmented Regression Analysis of 442 Mother–Infant Pairs

TL;DR

This study finds that late-pregnancy vitamin A levels have a nonlinear effect on newborn body proportions, with an optimal range of 0.65–1.65 μmol/L for best growth outcomes.

Contribution

The study identifies specific vitamin A thresholds and a triphasic relationship with neonatal ponderal index, challenging routine supplementation practices.

Findings

Maternal vitamin A levels between 0.65 and 1.65 μmol/L increase neonatal ponderal index by 0.47 kg/m³ per 0.5 μmol/L increment.

Vitamin A concentrations above 1.65 μmol/L decrease ponderal index, indicating a risk of overdose.

Male infants showed better growth parameters than females, and vitamin E supplementation increased birth weight by 401 g.

Abstract

The significance of vitamin A during pregnancy for fetal growth and development has garnered increasing attention. However, the dose–response relationship between vitamin A concentration in late pregnancy and the offspring's ponderal index (PI) remains unclear. This study aims to investigate this relationship and determine the optimal supplementation level of vitamin A, providing a scientific basis for clinical nutritional interventions. This study selected pregnant women and their offspring who voluntarily participated and established records at the Obstetrics Department of Shandong Second Medical University Affiliated Hospital from March 1, 2023, to September 1, 2024. A self‐designed questionnaire was utilized to collect demographic characteristics of the pregnant women, as well as factors influencing offspring growth. Fasting venous blood samples were collected from the pregnant women during late pregnancy (28 to 40 weeks), and high‐performance liquid chromatography (HPLC) was employed to measure serum concentrations of vitamins A, E, and C. Standard physical measurement methods were used to assess the offspring's birth weight and length. Data analysis was conducted using R programming language and EmpowerStats software, employing segmented linear regression analysis to determine the threshold of vitamin A concentration and its impact on PI. Analysis of 442 mother–infant pairs showed a nonlinear relationship between maternal vitamin A levels in the third trimester and the neonatal ponderal index (PI). An inverted U‐shaped curve was observed, with two key inflection points at 0.65 μmol/L (lower threshold) and 1.65 μmol/L (upper threshold). Within the optimal range of 0.65 to 1.65 μmol/L, each 0.5 μmol/L increase in vitamin A raised PI by 0.47 kg/m3 (95% CI: 0.42–0.52, p < 0.001), while concentrations above 1.65 μmol/L decreased PI (β = −0.44 per 0.5 μmol/L, 95% CI: −0.53 to −0.34, p < 0.001). This triphasic pattern remained consistent even after adjusting for 17 covariates, such as fetal sex, gestational age, and maternal nutritional status (adjusted R
2 = 0.81). Male infants consistently demonstrated superior growth parameters (+225 g weight, +0.40 cm length vs. females, p < 0.05), while maternal vitamin E supplementation independently increased birth weight by 401 g (p < 0.05). This study determines that the ideal range of maternal vitamin A during late pregnancy is 0.65–1.65 μmol/L for optimal neonatal growth. Levels above 1.65 μmol/L diminish growth benefits, whereas levels below 0.65 μmol/L restrict developmental potential. Our findings call into question the routine practice of vitamin A supplementation. Instead, we advocate for personalized monitoring to maintain the target range. This approach is vital for precision perinatal nutrition, as it helps prevent both growth restriction and the risks associated with vitamin overdose. This provides a valuable reference for nutritional health interventions during pregnancy.

This cohort study of 442 mother–infant pairs revealed a triphasic relationship between late‐pregnancy maternal vitamin A levels and neonatal ponderal index (PI), with optimal PI gains observed at 0.65–1.65 μmol/L (+0.47 kg/m3 per 0.5 μmol/L increment) but reversed effects beyond this therapeutic window. Threshold analysis demonstrated significant inflection points (0.65 μmol/L: β = 0.94, p < 0.001; 1.65 μmol/L: β = −0.44, p < 0.001), challenging current supplementation practices and advocating personalized monitoring to balance growth optimization with overdose risks.

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