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Threshold Effects of Third-Trimester Maternal Vitamin A on Neonatal Ponderal Index: A Segmented Regression Analysis
1Shandong Second Medical University Affiliated Hospital Weifang Shandong China.
Insights
Optimal vitamin A levels for pregnant women are between 0.65-1.65 μmol/L for healthy fetal growth. Higher or lower concentrations can negatively impact neonatal ponderal index (PI), emphasizing personalized monitoring over routine supplementation.
Area of Science:
- Perinatal nutrition
- Maternal-fetal medicine
- Developmental biology
Background:
- Vitamin A is crucial for fetal development, but its optimal concentration during late pregnancy and its effect on neonatal ponderal index (PI) are not well-defined.
- Understanding the dose-response relationship is essential for establishing evidence-based guidelines for prenatal vitamin A supplementation.
Purpose of the Study:
- To investigate the relationship between maternal serum vitamin A levels in late pregnancy and neonatal ponderal index (PI).
- To determine the optimal range of vitamin A supplementation for promoting healthy fetal growth and development.
Main Methods:
- A cohort study involving 442 mother-infant pairs, with data collected via questionnaires and serum vitamin A measurements using high-performance liquid chromatography (HPLC).
- Segmented linear regression analysis was used to identify thresholds and quantify the dose-response relationship between maternal vitamin A and neonatal PI.
- Covariates including fetal sex, gestational age, and maternal nutritional status were adjusted for in the analysis.
Main Results:
- A nonlinear, inverted U-shaped relationship was observed between maternal vitamin A levels and neonatal PI, with optimal levels between 0.65–1.65 μmol/L.
- Vitamin A concentrations within the optimal range positively correlated with PI, while levels above 1.65 μmol/L showed a negative impact on PI.
- Male infants exhibited significantly better growth parameters, and maternal vitamin E supplementation was associated with increased birth weight.
Conclusions:
- The ideal range for maternal vitamin A in late pregnancy is 0.65–1.65 μmol/L to ensure optimal neonatal growth.
- Current routine vitamin A supplementation practices may need re-evaluation in favor of personalized monitoring to avoid potential risks of overdose or deficiency.
- These findings support precision perinatal nutrition strategies to optimize fetal development and prevent adverse outcomes.
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.
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