BMI-Specific Gestational Weight Gain Thresholds to Minimize Small Vulnerable Newborn Risk in Underweight Chinese Women

BMI-Specific Gestational Weight Gain Thresholds to Minimize Small Vulnerable Newborn Risk in Underweight Chinese Women | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 9 October 2025 V1 Latest version Share on BMI-Specific Gestational Weight Gain Thresholds to Minimize Small Vulnerable Newborn Risk in Underweight Chinese Women Authors : Ziyi Song 0009-0009-2945-1052 , Li Zhang , Qing Fang , Jing Peng , Li Wu , Lulu Song , Lijuan Zheng , Guocheng Liu , Gaojie Fan [email protected] , Surong Mei , and Youjie Wang Authors Info & Affiliations https://doi.org/10.22541/au.176000615.54538913/v1 193 views 122 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background : Maternal underweight elevates small vulnerable newborn (SVN) risk, yet optimal BMI-specific gestational weight gain (GWG) thresholds remain undefined, challenging uniform recommendations for underweight pregnancies. Objective: To quantify how severity of maternal underweight modifies SVN risk, and to determine BMI-specific GWG thresholds that minimize this risk in underweight Chinese women. Methods: In this retrospective cohort study, 23,392 singleton pregnancies with maternal underweight were analyzed from 141,163 deliveries at Guangdong Women and Children Hospital between 1 January 2015 and 30 June 2024. Underweight was graded as Grade 1 (17.5–<18.5 kg/m 2 ), Grade 2 (16–<17.5 kg/m 2 ), or Grade 3 (<16.0 kg/m 2 ). GWG was calculated as weight before delivery minus pre-pregnancy weight. Modified Poisson regression estimated adjusted rate ratios (RRs) for SVN across GWG categories. Restricted cubic splines and two-piecewise models assessed non-linearity and threshold effects. Results: SVN incidence rose dose-dependently with underweight severity: 18.8 % (Grade 1), 23.2 % (Grade 2), and 30.6 % (Grade 3). GWG exhibited a non-linear inverse relationship with SVN risk (P<0.001). Threshold analysis identified BMI-specific optimal GWG: 15.0 kg (Grade 1), 16.3 kg (Grade 2) and 21.5 kg (Grade 3). Two-piece regression revealed each additional kilogram increase in GWG up to these thresholds reduced SVN risk by 8–11 % (RR: 0.89–0.92), further gains above the thresholds conferred no additional benefit. Conclusions: Current uniform recommendation of GWG for underweight women are insufficient for severe underweight. Grade-specific targets particularly 21.5 kg for BMI <16 kg/m 2 are required to minimize SVN risk. Prospective validation and mechanistic studies are warranted to integrate these thresholds into precision prenatal care. BMI-Specific Gestational Weight Gain Thresholds to Minimize Small Vulnerable Newborn Risk in Underweight Chinese Women Ziyi Song 1 2 #, Li Zhang 1 #, Qing Fang 2 , Jing Peng 1 , Li Wu 1 , Lulu Song 2 , Lijuan Zheng 1 , Guocheng Liu 1 *, Gaojie Fan 2 *, Surong Mei 2 , Youjie Wang 2 # These two authors contributed equally to this work. * Corresponding author 1 Guangdong Women and Children Hospital, No. 521 Xingnan Avenue, Guangzhou, 511400, China 2 Department of Maternal and Child Health, School of Public Health, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, China * Correspondence: Guocheng Liu, Email: [email protected] * Correspondence: Gaojie Fan, Email: [email protected] Abstract Background : Maternal underweight elevates small vulnerable newborn (SVN) risk, yet optimal BMI-specific gestational weight gain (GWG) thresholds remain undefined, challenging uniform recommendations for underweight pregnancies. Objective: To quantify how severity of maternal underweight modifies SVN risk, and to determine BMI-specific GWG thresholds that minimize this risk in underweight Chinese women. Methods: In this retrospective cohort study, 23,392 singleton pregnancies with maternal underweight were analyzed from 141,163 deliveries at Guangdong Women and Children Hospital between 1 January 2015 and 30 June 2024. Underweight was graded as Grade 1 (17.5–<18.5 kg/m²), Grade 2 (16–<17.5 kg/m²), or Grade 3 (<16.0 kg/m²). GWG was calculated as weight before delivery minus pre-pregnancy weight. Modified Poisson regression estimated adjusted rate ratios (RRs) for SVN across GWG categories. Restricted cubic splines and two-piecewise models assessed non-linearity and threshold effects. Results: SVN incidence rose dose-dependently with underweight severity: 18.8 % (Grade 1), 23.2 % (Grade 2), and 30.6 % (Grade 3). GWG exhibited a non-linear inverse relationship with SVN risk (P<0.001). Threshold analysis identified BMI-specific optimal GWG: 15.0 kg (Grade 1), 16.3 kg (Grade 2) and 21.5 kg (Grade 3). Two-piece regression revealed each additional kilogram increase in GWG up to these thresholds reduced SVN risk by 8–11 % (RR: 0.89–0.92), further gains above the thresholds conferred no additional benefit. Conclusions: Current uniform recommendation of GWG for underweight women are insufficient for severe underweight. Grade-specific targets particularly 21.5 kg for BMI <16 kg/m² are required to minimize SVN risk. Prospective validation and mechanistic studies are warranted to integrate these thresholds into precision prenatal care. Abbreviations: CI: confidence intervalGDM: gestational diabetes mellitusGWG: gestational weight gainHDP: hypertensive disorders of pregnancyLGA: large for gestational ageLBW: low birth weightPTB: preterm birthRCS: restricted cubic splinesRR: rate ratioSGA: small for gestational ageSVN: small vulnerable newborn Keywords : maternal underweight; small vulnerable newborn; gestational weight gain; BMI-specific thresholds; modified Poisson regression Introduction Despite escalating global prevalence of maternal overweight and obesity, pre-pregnancy underweight remains public health concern, particularly in low-income countries and Eastern Asian regions such as Japan, South Korea and China 1-4 . A meta-analysis of over one million pregnancies indicates a geographic gradient, with pre-pregnancy underweight prevalence of 5% in the USA, 3% in Europe, and 17% across Asia 5 . In China, this burden exhibits striking heterogeneity, affluent regions like Beijing (12.2%) 6 and Shanghai (15.0%) 7 reported unexpectedly high rates despite minimal food insecurity. Nationally, the pre-pregnancy underweight prevalence (13.37%) substantially exceeds obesity (2.89%), highlighting its persistent burden 8 . Pre-pregnancy underweight is a well-established risk factor for adverse neonatal outcomes 9-11 , including small for gestational age (SGA), low birth weight (LBW), and preterm birth(PTB). These condition are now unified under the new concept of small vulnerable newborn (SVN) 12 , which encompasses infants facing elevated mortality risks, developmental delays, and lifelong susceptibility to metabolic and cardiovascular diseases 12, 13 . Crucially, risk severity correlates with underweight severity. Studies demonstrate a dose-response relationship, wherein progressively lower maternal BMI exacerbates risk of PTB, LBW, and SGA 2, 14 However, existing evidence fails to address whether adequate gestational weight gain (GWG) can mitigate these risks across underweight severity strata. Optimal maternal nutrition during pregnancy is essential for supporting fetal growth and newborn health 15, 16 , GWG serves as key indicator of maternal nutritional status during pregnancy, and adequate GWG is critical for counteracting pre-pregnancy nutritional deficits 17 . Current guidelines, such as those from the Institute of Medicine (IOM, now the National Academy of Medicine) recommend a uniform range of 12.5-18 kg for all underweight women (BMI<18.5 kg/m²) 18 . Yet emerging data suggest this one-size-fits-all approach may be suboptimal. International variations in recommendations and emerging data suggest that optimal GWG may differ by underweight severity, women with severe underweight (BMI nutrient deficits, while moderately underweight women may benefit from intermediate targets 19, 20 . This gap is compounded by evidence supporting stratified GWG thresholds for other BMI categories (e.g., obesity), 21 , highlighting the need for precision guidelines tailored to underweight severity. To address these gaps, this study uses prenatal and delivery data from 23,392 underweight Chinese women (BMI <18.5 kg/m²). We aim to quantify differential SVN risks across pre-pregnancy underweight severity strata, and identify BMI-specific optimal GWG thresholds to minimize SVN risk. Methods Study design and population This retrospective cohort study utilized data from the Guangdong Women and Children Hospital Information System, which contains comprehensive electronic medical records, including demographic characteristics, prenatal visit data, and delivery admission records. A total of 141,163 women with singleton pregnancies who received prenatal examination and delivered between 1 January 2015 and 30 June 2024 were retrieved from the information system. We excluded 19,618 women lacking data on weight or height to calculate pre-pregnancy BMI and gestational weight gain, 17,491 women with pre-pregnancy BMI ≥24 kg/m² (Asian-specific overweight threshold) and 10 women with missing birth weight data. After exclusion, a total of 104,044 women with pre-pregnancy BMI <24 kg/m² were retained for analysis. Within this cohort, 80,652 women with normal weight (BMI 18.5–<24 kg/m²), 23,392 women with pre-pregnancy BMI <18.5 kg/m² (underweight) formed the subgroup for primary outcome assessment. 23,392 women (BMI <18.5 kg/m²) further classified as grade 1 underweight (BMI 17.5–<18.5 kg/m²), grade 2 underweight (16.0–<17.5 kg/m²) and grade 3 underweight (BMI 22 .Flowchart of the study presented in Figure S1 . Ethical approval was obtained from the Institutional Review Board of Guangdong Women and Children Hospital, with waived informed consent for de-identified data. Exposure assessment Pre-pregnancy BMI was calculated as self-reported pre-pregnancy weight (kg) divided by height (cm) measured at the first prenatal visit. Gestational weight gain (GWG) was computed as the difference between the final weight measured before delivery and self-reported pre-pregnancy weight. Outcome definition The primary outcome was small vulnerable newborns (SVN), a composite endpoint defined as the presence of any of: Preterm birth（PTB）: Delivery <37 gestational weeks; Low birth weight (LBW): Birthweight <2,500g; Small-for-gestational-age (SGA): Sex-specific birthweight <10th percentile for gestational age, per Chinese national standards 23 . The secondary outcomes were: Large-for gestational-age(LGA): Sex-specific birthweight ≥10th percentile for gestational age, per Chinese national standards 23 ; Gestational diabetes mellitus (GDM) was diagnosed based on 75-g oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation using diagnostic thresholds of International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria 24 . GDM is diagnosed if any one value meets or exceeds these levels: fasting plasma glucose: ≥5.1 mmol/L, 1-hour post-glucose load: ≥10.0 mmol/L, 2-hour post-glucose load: ≥8.5 mmol/L. Hypertensive disorders of pregnancy (HDP) were diagnosed by obstetricians in the study hospital during the prenatal visit according to the diagnostic criteria from the Chinese Society of Obstetrics and Gynecology. 25 Covariates The following covariates were extracted from medical records: maternal age, parity (nulliparous/multiparous), educational attainment (Junior high school or below, Senior high school, College or above), infant sex (male, female). Statistical Analysis Continuous variables were summarized as means ± standard deviations (SD), and categorical variables as frequencies and percentages. Group comparisons used Chi-squared tests for categorical variables and one-way ANOVA for continuous variables. To quantify associations between GWG and SVN risk across underweight strata, we fitted modified Poisson regression models to generate adjusted rate ratios (RRs) and 95% confidence intervals (CIs), controlling for pre-pregnancy BMI, age, parity, education level, GDM, HDP, and infant sex. Nonlinear relationships were assessed using restricted cubic splines (RCS) with three knots (10th, 50th, and 90th percentiles of GWG). The reference gestational weight gain (GWG) was set at 12.5 kg, corresponding to the lower bound of the range recommended by the Institute of Medicine (IOM) for underweight women. Upon confirmation of nonlinear relationship by RCS (likelihood ratio test P<0.05), a two-piecewise modified Poisson regression model was used to explore potential threshold effects. The threshold value was determined by testing all possible GWG values and selecting the point with the highest likelihood. Statistical significance of trends across BMI groups (normal, underweight grade 1, underweight grade 2, underweight grade 3) and gestational weight GWG categories (insufficient, optimal, excessive) was assessed using the Cochran-Armitage trend test. All statistical analyses were performed using R software. A P < 0.05 was considered statistically significant. Results A total of 104,044 women with pre-pregnancy BMI <24 kg/m² were included in this retrospective cohort study. Of these 80,652 (77.5%) had normal weight (BMI 18.5 –< 24 kg/m²), while 23,392 (22.5%) were underweight (BMI <18.5 kg/m²). Among the underweight participants, 13 725 (58.7%) were classified as had grade 1 underweight (BMI 17.5–< 18.5 kg/m²), 8354 (35.7%) as grade 2 underweight (BMI 16.0–<17.5 kg/m²), and 1313(5.6%) as grade 3 underweight (BMI <16.0 kg/m²) based on WHO classification. Table 1 presents the characteristics of 104,044 study population stratified by pre-pregnancy BMI status. Compared to normal weight women, underweight women were younger and more likely to be nulliparous. Underweight women exhibited higher mean gestational weight gain (14.21 ± 4.09 kg vs. 13.77 ± 4.48 kg), with a higher rate of optimal weight gain (51.1% vs. 41.3%) and a lower rate of excessive gain (18.5% vs. 31.6%). Table 1. Basic characteristic of the study participants stratified by pre-pregnancy BMI Age * 30.51 ± 4.47 28.52 ± 4.06 28.82 ± 4.11 28.18 ± 3.97 27.59 ± 3.85 Parity (%) * Nulliparous 40424 (50.1) 14619 (62.5) 8387 (61.1) 5353 (64.1) 879 (66.9) Multiparous 40224 (49.9) 8772 (37.5) 5338 (38.9) 3000 (35.9) 434 (33.1) Gestational age (week) 38.71 ± 1.64 38.70 ± 1.59 38.73 ± 1.56 38.67 ± 1.63 38.52 ± 1.59 Education (%) Junior school or below 7559 (11.8) 2198 (11.8) 1282 (11.8) 787 (11.9) 129 (12.3) High school 14201 (22.2) 4255 (22.9) 2469 (22.6) 1541 (23.2) 245 (23.4) College or above 42348 (66.1) 12141 (65.3) 7159 (65.6) 4310 (64.9) 672 (64.2) Infant sex Male 43263 (53.6) 12446 (53.2) 7308 (53.2) 4444 (53.2) 694 (52.9) Female 37389 (46.4) 10946 (46.8) 6417 (46.8) 3910 (46.8) 619 (47.1) Pre-pregnancy BMI (kg/m 2 ) 20.85 ± 1.47 17.48 ± 0.82 18.04 ± 0.29 16.90 ± 0.41 15.42 ± 0.49 GWG (kg) * 13.77 ± 4.48 14.21 ± 4.09 14.23 ± 4.08 14.22 ± 4.10 14.08 ± 4.11 GWG on IOM criteria(%) * Insufficient 21881 (27.1) 7127 (30.5) 4097 (29.9) 2605 (31.2) 425 (32.4) Optimal 33318 (41.3) 11943 (51.1) 7100 (51.7) 4211 (50.4) 632 (48.1) Excessive 25453 (31.6) 4322 (18.5) 2528 (18.4) 1538 (18.4) 256 (19.5) PTB (%) 5130 (6.4) 1468 (6.3) 803 (5.9) 564 (6.8) 101 (7.7) SGA (%) * 7436 (9.9) 3629 (16.0) 1860 (14.1) 1450 (17.9) 319 (24.8) LBW * 4698 (6.0) 1779 (7.7) 911 (6.7) 708 (8.6) 160 (12.2) SVN * 11643 (15.5) 4763 (21.0) 2484 (18.8) 1884 (23.2) 395 (30.6) LGA(%) * 5832 (7.2) 773 (3.3) 515 (3.7) 233 (2.8) 25 (1.9) GDM (%) * 13725 (17.0) 2384 (10.2) 1469 (10.7) 782 (9.4) 133 (10.1) HDP (%) * 3043 (3.8) 508 (2.2) 291 (2.1) 183 (2.2) 34 (2.6) Statistically significant difference in characteristic between women with normal weight and underweight. normal weight (BMI 18.5 to <24 kg/m2), underweight grade 1 (BMI 17.5 to <18.5 kg/m2); underweight grade 2 (BMI 16.0 to <17.5 kg/m2); underweight grade 3 (BMI < 16.0 kg/m2). PTB rate was lowest in the underweight grade 1 group (5.9%), and highest in underweight grade 3 group. The rate of SGA, LBW and SVN increased progressively with the severity of pre-pregnancy underweight, while the rate of LGA decreased progressively with the severity of pre-pregnancy underweight. Regarding pregnancy complication, underweight women had lower rate of GDM and HDP. Table 2 shows the rate of SVN and its composites (PTB, SGA, LBW) across different pre-pregnancy BMI status and GWG categories among normal weight and underweight women. The analysis demonstrated a dose-dependent relationship between pregnancy normal weight and underweight severity (grade 1 through grade 3) and an increasing incidence of SVN, its composite of SGA and LBW, regardless of GWG group ( all P for trend < 0.001) . The elevated SVN rate is consistently highest among women with insufficient GWG, and escalated markedly with severity of underweight across all measured outcomes (SGA, LBW and PTB). For underweight grade 1, the rate of SVN was highest in the insufficient GWG group (25.3%), followed by optimal GWG (15.8%) and excessive GWG (12.9%). Similar trends were observed for underweight grade 2 and grade 3. PTB, SGA, and LBW also showed higher rates in the insufficient GWG group across all underweight grades. Overall, the rate of SVN and its composites increased with higher underweight grades and insufficient GWG. The highest rate of SVN (41.2%) and its composites of PTB (9.7%), SGA (34.3%）and LBW (18.6%) were observed in the groups with underweight grade 3 and insufficient GWG. Table 2. Rate of SVNs stratified by pre-pregnancy BMI and GWG categories Small vulnerable newborns, n (%) Insufficient GWG 4215 (19.3) 1038 (25.3) 848 (32.6) 175 (41.2) < 0.001 Optimal GWG 4505 (13.5) 1119 (15.8) 806 (19.1) 175 (27.7) < 0.001 Excessive GWG 2923 (11.5) 327 (12.9) 230 (15.0) 45 (17.6) < 0.001 P for trend < 0.001 < 0.001 < 0.001 < 0.001 Preterm birth, n (%) Insufficient GWG 1675 (7.7) 318 (7.8) 238 (9.1) 41 (9.7) 0.01 Optimal GWG 1943 (5.8) 335 (4.7) 226 (5.4) 43 (6.8) 0.07 Excessive GWG 1512 (5.9) 150 (5.9) 100 (6.5) 17 (6.6) 0.38 P for trend < 0.001 < 0.001 < 0.001 0.11 SGA, n (%) Insufficient GWG 2840 (13.0) 788 (19.2) 667 (25.6) 146 (34.3) < 0.001 Optimal GWG 2897 (8.7) 851 (12.0) 627 (14.9) 143 (22.6) < 0.001 Excessive GWG 1699 (6.7) 221 (8.74) 156 (10.1) 30 (11.7) < 0.001 P for trend < 0.001 < 0.001 < 0.001 < 0.001 Low birthweight, n (%) Insufficient GWG 1731 (7.9) 412 (10.1) 317 (12.2) 79 (18.6) < 0.001 Optimal GWG 1739 (5.2) 360 (5.1) 285 (6.8) 62 (9.8) < 0.001 Excessive GWG 1228 (4.8) 139 (5.5) 106 (6.9) 19 (7.4) < 0.001 P for trend < 0.001 < 0.001 < 0.001 < 0.001 Based on the analysis of 104,044 pregnant women presented in Table S1 , LGA rate demonstrated a strong positive association with GWG while exhibiting an inverse relationship with underweight severity (P for trend <0.001) as evidenced by the highest LGA rates occurring in excessive GWG groups (e.g., normal-weight: 11.9%, grade 3 underweight: 5.5%) and the lowest in severe underweight with insufficient GWG (0.5%). HDP consistently showed elevated rates with excessive GWG across all BMI categories (e.g., normal-weight: 5.4%, grade 3 underweight: 5.1%). However, the counterintuitive finding of consistently higher GDM rates in insufficient GWG groups across all BMI strata (e.g., insufficient GWG: 28.0% vs. excessive: 10.3% in normal weight group; insufficient GWG: 18.1% vs. excessive: 7.0% in grade 3 underweight group). This phenomenon may be explained by the clinical sequence of GDM management. GDM is diagnosed via oral glucose tolerance testing (OGTT) at 24-28 gestational weeks, prompting intensive lifestyle interventions (e.g., calorie restriction, carbohydrate control, physical activity) as first-line therapy 26 , consequently, suboptimal weight gain reflects a medically induced outcome of GDM treatment rather than a causative factor for GDM development. Figure 1 illustrates the non-linear association between GWG and the relative risk of SVNs via restricted cubic splines (RCS) modeled with modified Poisson regression. The regression models were adjusted for confounders including pre-pregnancy BMI, age, parity, education level, GDM, HDP, and infant sex. Across all groups (overall underweight and stratified by underweight severity grades 1-3), the curves exhibited a similar pattern of significant risk reduction (all P for overall and non-linearity <0.001): RR decreased steeply as GWG increased up to approximately 20 kg, followed by a plateau at higher GWG levels, suggesting a threshold effect above which additional weight gain minimally reduced SVN risk. The relationship was most pronounced in women with grade 3 underweight, where achieving GWG beyond the reference point markedly lowered SVN risk. Figure 1 RCS curve of GWG and risk of SVNs. The RCS curve was s constructed using a modified Poisson regression model adjusting for pre-pregnancy BMI, age, parity, education level, GDM, HDP, and infant sex. Three knots were placed at the 10th, 50th, and 90th percentiles of the distribution of GWG. The reference point was the lower limit of the IOM recommendation (12.5 kg). The red line and red shaded region represents the RR and the 95% CI bounds, respectively. A two piecewise modified Poisson regression model was used to identify threshold association between GWG and SVN risk, as well as to determine the threshold value of GWG, the results were presented in Table 3 . The optimal GWG thresholds were 16.9 kg for the overall underweight population, 15.0kg for grade 1, 16.3kg for grade 2, 21.5 kg grade 3 underweight. The results of modified Poisson regression further demonstrated that among the overall underweight population, each 1-kg increase up to GWG ≤16.9 kg was associated with a 9% reduction in SVN risk (RR=0.91, 95% CI 0.90–0.92), whereas GWG exceeding this threshold showed no significant protective effect (RR=0.99, 95% CI 0.97–1.01). Grade-specific analyses further revealed: for grade 1 underweight, each 1-kg increase up to 15.0 kg GWG conferred a 10% risk reduction in SVN (RR=0.90, 95% CI 0.89–0.92); For grade 2 underweight, each 1-kg increase up to 16.3 kg GWG yielded an 11% reduction in SVN (RR=0.89, 95% CI 0.88–0.91); For grade 3 underweight, each 1-kg increase up to 21.5 kg GWG provided an 8% reduction in SVN (RR=0.92, 95% CI 0.90–0.94). All models were adjusted for maternal pre-pregnancy BMI, age, parity, education, GDM, HDP, and infant sex. Table 3. Threshold effects of GWG on SVN: Two-piecewise regression Overall: 16.9 kg GWG ≤ 16.9 kg 17105 0.91 (0.90, 0.92) 16.9 kg 6287 0.99 (0.97, 1.01) 0.28 Underweight grade 1: 15.0 kg GWG ≤ 15.0 kg 7783 0.90 (0.89, 0.92) 15.0 kg 5942 0.98 (0.96, 1.01) 0.13 Underweight grade 2: 16.3 kg GWG ≤ 16.3 kg 5813 0.89 (0.88, 0.91) 16.3 kg 2641 0.99 (0.96, 1.02) 0.37 Underweight grade 3: 21.5 kg GWG ≤ 21.5 kg 1236 0.92 (0.90, 0.94) 21.5 kg 77 1.12 (0.99, 1.26) 0.06 Model was adjusted for pre-pregnancy BMI, age, parity, education level, GDM, HDP, and infant sex. Discussion In this large retrospective cohort study of 23,392 underweight Chinese women, we found that that pre-pregnancy underweight severity and GWG are critical determinants of SVN risk. We identified a pronounced dose-dependent gradient that SVN rate rose with the severity of in underweight (grade 1 to grade 3). Crucially, insufficient GWG amplified SVN risk across all underweight grades, with the most severe impact in in grade 3 underweight women, driving SGA rate to 34.3% and SVN to 41.2%. Conversely, excessive GWG exerted a protective effect against SVN in underweight women, diverging from the established risks associated with excessive gain in higher BMI categories. Most significantly, our threshold analysis established BMI-stratified optimal GWG targets, 15.0 kg for grade 1, 16.3 kg for grade 2, and 21.5 kg for grade 3 underweight, providing evidence-based precision guidance for clinical practice. Our findings align with global evidence linking underweight to SVN risk, especially the SGA and LBW. 10 11 27 . but extend it by quantifying severity-specific GWG thresholds. While current guidelines, recommend a uniform GWG range for all underweight women (BMI <18.5 kg/m²). Our study suggests that such a ”one-size-fits-all” approach fails to address the heterogeneous needs of underweight subpopulations. Our findings revealed that underweight women, especially those with severe underweight require significantly higher GWG to minimize SVN risk, exceeding IOM’s upper limit (18kg) by 19.4% or upper limit of Chinese guideline (16.0 kg) by 34.3% 28 . Compensatory GWG must not only support fetal growth but also replenish maternal reserves. Severely underweight women (BMI <16.0 kg/m²) typically exhibit profound depletion of energy reserves and micronutrient deficiencies, which impair placental angiogenesis and fetal nutrient supply and cause the adverse birth outcomes. 29 Our finding of severity-specific GWG for underweight women is similar to research conducted among pregnant women with obesity 21 , which demonstrated that a single, universal lower limit for GWG proves inadequate for the obese population, and suggested to remove or lower the lower limit of current IOM recommendations and separate guidelines for severe or class 3 obesity（BMI≥40 kg/m2）women. Our data indicate that underweight women, especially those with lower BMI classifications, require appropriately higher within the existing recommendation range. This compelling evidence underscores the crucial principle that GWG guidelines must be stratified according to both ends of the maternal pre-pregnancy BMI spectrum, acknowledging that optimal weight gain is contingent upon the specific degree of underweight or obesity to improve maternal and infant outcomes. Although our proposed GWG thresholds for SVN prevention in underweight women exceed the upper limits of IOM and Chinese guidelines, potentially elevating risks associated with excessive weight gain, such as LGA, HDP, GDM, and the increased childhood obesity risk in offspring 30-32 , a critical risk-benefit assessment favors higher GWG in this cohort. Our analysis revealed that excessive GWG elevates adverse outcomes such as LGA, HDP ( Table S1 ), yet absolute risks in underweight women remain markedly lower than normal-weight counterparts even at high GWG. For instance, grade 3 underweight women with excessive GWG exhibited only 5.5% LGA and 5.1% HDP rates, well below the 11.9% (LGA) and 5.4% (HDP) observed in normal-weight women with equivalent GWG. More critically, the absolute increase in LGA risk induced by excessive GWG (e.g., +4.1%, in grade 3 underweight) is substantially outweighed by the magnitude of SGA reduction achieved through excessive GWG gain (e.g., -10.9% in the same subgroup). This priority is aligns with a Delphi consensus study rating SGA severity at 40 points versus 30 points for LGA 33 , reflecting that preventing SGA-linked metabolic disorders in later life or irreversible neurodevelopmental impairments holds greater clinical urgency than mitigating LGA-related complications. Simultaneously, excessive GWG drove a profound, dose-dependent reduction in SVN incidence, particularly in severe underweight where SVN risk decreased sharply. The disproportionate burden of SVN outweighs the modest incremental risks of GDM/HDP in underweight women, especially given their inherently lower metabolic risk profile. Thus, prioritizing SVN prevention through tailored GWG thresholds is clinically warranted, with future guidelines needing BMI-specific stratification to optimize trade-offs. Furthermore, in pre-pregnancy underweight mothers, excessive GWG mitigates postpartum undernutrition by sustaining vital reserves despite potential weight retention. While food scarcity-driven malnutrition has declined in recent decades, pre-pregnancy underweight remains alarmingly prevalent across low- and middle-income countries, affecting 15-30% of women in regions like South Asia and Sub-Saharan Africa 4 . Conversely, in high-income East Asian societies, notably Japan 1 , South Korea 34 and alongside China (an upper-middle income economy), an cultural preferences for thinness have normalized BMI<18.5 kg/m² among young women, driving underweight rates exceeding 15% in urban cohorts. Our severity-stratified GWG thresholds thus provide actionable solutions for two distinct epidemiological scenarios. In LMICs, where fetal growth restriction remains endemic, implementing our thresholds via community-based antenatal programs could avert SVN cases by redirecting scarce nutritional resources to the most vulnerable (Grade 3 underweight women requiring >21.5 kg GWG). In East Asian settings, our findings counter deeply entrenched “thinness norms” by demonstrating that underweight women, particularly those with BMI<16.0, biologically require substantially higher GWG than current guidelines. Clinic-ready inflection points (e.g., 21.5 kg for Grade 3) offer concrete targets for prenatal counseling to overcome resistance to healthy weight gain. Strengths of this study include the large sample size (n=23,392), granular underweight stratification (Grades 1–3), and advanced statistical methods (restricted cubic splines, two piecewise regression) for objective threshold identification. However, limitations must be acknowledged. First, self-reported pre-pregnancy weight may introduce recall bias, though height was objectively measured; Second, residual confounding by unmeasured factors (e.g., micronutrient status, diet quality) could influence SVN risk. Crucially, data on the specific causes of maternal underweight; information on pathological conditions such as anorexia nervosa was unavailable, although its prevalence among young Chinese women is known to be low 35 . Third, the single-region cohort (Guangzhou, China, a southern city with higher underweight prevalence) may limit generalizability to populations with distinct genetic, lifestyle, or environmental backgrounds. Fourth, short-term focus on SVN, omitted long-term maternal-infant outcomes (e.g., postpartum weight retention, cardiometabolic disease linked to GWG). Conclusion This study establishes that underweight severity modifies GWG efficacy in SVN prevention. The IOM’s uniform GWG range (12.5–18 kg) is inadequate for severely underweight women, who require GWG up to 21.5 kg to minimize SVN risk. Future research should validate these thresholds prospectively and explore nutrient-partitioning mechanisms linking higher GWG to fetal protection in underweight women. Acknowledgements Author Contributions The authors’ responsibilities were as follows: ZS, GF, GL designed research, LZ, QF, JP, LW, LS, LZ, GL provided the database; ZS and GF analyzed data, ZS, LZ wrote the manuscript; YW reviewed and edited the manuscript, GL all GF had primary responsibility for final content; and all authors have read and approved the final manuscript Data Availability * : The de-identified datasets generated or analyzed for this study from the corresponding authors upon reasonable request. Funding: This work was supported by the National Key Research and Development Program of China (2021YFA1101500), National Natural Science Foundation of China (82003479, 82073660). Author Disclosures: The authors report no conflicts of interest Declaration of Generative AI and AI-assisted technologies in the writing process: During the preparation of this work the author(s) used DeepSeek in order to improve the language clarity and grammar for non-native English writing. 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Keywords developing countries: obstetrics and gynaecology epidemiology: general obstetric general obstetrics Authors Affiliations Ziyi Song 0009-0009-2945-1052 Guangdong Women and Children Hospital View all articles by this author Li Zhang Guangdong Women and Children Hospital View all articles by this author Qing Fang Huazhong University of Science and Technology Department of Maternal and Child Health View all articles by this author Jing Peng Guangdong Women and Children Hospital View all articles by this author Li Wu Guangdong Women and Children Hospital View all articles by this author Lulu Song Huazhong University of Science and Technology Department of Maternal and Child Health View all articles by this author Lijuan Zheng Guangdong Women and Children Hospital View all articles by this author Guocheng Liu Guangdong Women and Children Hospital View all articles by this author Gaojie Fan [email protected] Huazhong University of Science and Technology Department of Maternal and Child Health View all articles by this author Surong Mei Huazhong University of Science and Technology Department of Maternal and Child Health View all articles by this author Youjie Wang Huazhong University of Science and Technology Department of Maternal and Child Health View all articles by this author Metrics & Citations Metrics Article Usage 193 views 122 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ziyi Song, Li Zhang, Qing Fang, et al. 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