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A growing number of epidemiologic studies have estimated the associations between endocrine-disrupting chemicals and gestational diabetes mellitus (GDM). However, reports on the association between bisphenol A (BPA) substitutes and GDM are limited. This investigation aimed to explore the associations of maternal serum BPA, bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) with the risk of GDM. A nested case–control study was performed among 500 pregnant women. In conditional logistic regression models, the OR for BPS was significantly increased in the medium exposure groups (OR = 1.77; 95% CI: 1.01, 3.13) compared with the reference group, while BPA (OR: 0.38, 95%CI: 0.29, 0.50) and TBBPA (OR: 0.67, 95%CI: 0.54, 0.85) were negatively associated with the risk of GDM. In the Bayesian kernel machine regression (BKMR) analysis, the joint effect of bisphenols was positively associated with the risk of GDM. BPS showed positively relationship, while BPA and TBBPA showed negatively relationship, respectively. The quantile g-computation revealed a statistically significant and negative joint effect of the five bisphenols on the risk of GDM (OR: 0.57; 95% CI: 0.46, 0.72) with BPA (70.2%), TBBPA (21.3%), and BPB (8.5%) had positive contribution to the overall effect. These findings suggested that BPS had a positive effect on the risk of GDM, while BPA and TBBPA had negative effect on the risk of GDM. Moreover, exposure to the mixture of the five bisphenols was negatively associated with the risk of GDM. [ABSTRACT FROM AUTHOR]

Bisphenols are endocrine disruptor chemicals that disrupt thyroid hormone homeostasis. However, evidence on the effects of bisphenol mixtures on thyroid hormones are insufficient. Therefore, the present study aimed to explore the effects of bisphenol substitutes and bisphenol mixtures on thyroid hormones during pregnancy. The study was conducted among 446 pregnant women in the Guangxi Zhuang Birth Cohort (GZBC), China. In multiple linear regressions, compared with the low-exposure group, bisphenol S (BPS) concentrations in the middle-exposure group led to a 10.90% (95% CI: − 18.16%, − 2.99%) decrease in triiodothyronine (T3) levels in the first trimester; tetrabromobisphenol A (TBBPA) levels in the middle-exposure group led to an 8.26% (95% CI: − 15.82%, − 0.01%) decrease in T3 levels in the first trimester; bisphenol B (BPB) levels in the middle-exposure group led to higher free thyroxine (FT4) levels (9.84%; 95% CI: 1.73%, 18.60%) in the second trimester; bisphenol F (BPF) in the middle-exposure group led to higher FT4 levels (8.59%, 95% CI: 0.53%, 17.31%) in the second trimester; and TBBPA levels in the high-exposure group led to a 9.39% (95% CI: 1.46%, 17.93%) increase in FT4 levels in the second trimester. The Bayesian kernel machine regression (BKMR) and restricted cubic spline (RCS) models showed a U-shaped dose–response relationship between bisphenol A (BPA) and free triiodothyronine (FT3) (p < 0.01) as well as BPS and FT4 (p < 0.05). Nonlinear relationships were also observed between the bisphenol mixture and FT3. Overall, maternal bisphenol exposure affected thyroid hormone levels during pregnancy. This study provides evidence that BPB, BPF, BPS, and TBBPA are unsafe substitutes for BPA, as well as the overall effect of bisphenols on adverse health in human beings. [ABSTRACT FROM AUTHOR]

Phthalates (PAEs) are common endocrine disrupting chemicals (EDCs) that disrupt fetal development. The present study aimed to evaluate the effects of single and coexposure to phthalates in early pregnancy on fetal growth restriction (FGR) by a nested case–control study based on the Guangxi Zhuang Birth Cohort (GZBC). Maternal serum concentrations of seven phthalates in 97 neonates with FGR and 291 matched controls were detected through gas chromatography–mass spectrometry (GC–MS). The associations between phthalates and FGR were analyzed using multiple logistic regression, weight quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. We found that exposures to butyl-benzyl phthalate (BBP, ORadj = 1.849, 95% CI: 1.080–3.177, Padj = 0.025, Ptrend = 0.046), di (2-ethyl-hexyl) phthalate (DEHP, ORadj = 3.893, 95% CI: 1.305–11.910, Padj = 0.015, Ptrend = 0.098) and dimethyl phthalate (DMP, ORadj = 1.722, 95% CI: 1.089–2.725, Padj = 0.020, Ptrend = 0.002) were significantly positively associated with the risk of FGR, while mono-butyl phthalate (MBP) showed a significant negative association with FGR (ORhigh = 0.192, 95% CI: 0.036–0.795, Padj = 0.033, Ptrend = 0.035) only among girls. The WQS model identified that BBP, di(2-ethyl)phthalate (DEP), DMP, DEHP, di-n-butyl phthalate (DBP), and MBP were highly weighted in the association with FGR. The BKMR model supported the positive association between joint exposure to phthalates and the risk of FGR and identified no significant interaction between the seven phthalates. Overall, maternal exposure to BBP, DEHP, and DMP may cause adverse effects on FGR, especially with combined effects. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction (IUGR) is an abnormal fetal growth pattern that can lead to neonatal morbidity and mortality. IUGR may be affected by prenatal exposure to environmental pollutants, including perfluoroalkyl substances (PFASs). However, research linking PFAS exposure to IUGR is limited, with inconsistent results. We aimed to investigate the association between PFAS exposure and IUGR by using nested case control study based on Guangxi Zhuang Birth Cohort (GZBC), in Guangxi, China. A total of 200 IUGR cases and 600 controls were enrolled in this study. The maternal serum concentrations of nine PFASs were measured using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC MS). The associations single and mixed effects of prenatal PFAS exposure on IUGR risk were assessed using conditional logistic regression (single-exposure), Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models. In the conditional logistic regression models, the log10-transformed concentrations of perfluoroheptanoic acid (PFHpA, adjusted OR: 4.41, 95% CI: 3.03–6.41), perfluorododecanoic acid (PFDoA, adjusted OR: 1.94, 95% CI: 1.14–3.32), and perfluorohexanesulfonate (PFHxS, adjusted OR: 1.83, 95% CI: 1.15–2.91) were positively associated with risk of IUGR. In the BKMR models, the combined effect of PFASs was positively associated with IUGR risk. In the qgcomp models, we also found an increased IUGR risk (OR=5.92, 95% CI: 2.33–15.06) when all nine PFASs increased by one tertile as a whole, and PFHpA (43.9%) contributed the largest positive weights. These findings suggested prenatal exposure to single and mixtures of PFASs may increase IUGR risk, with the effect being largely driven by the PFHpA concentration. [Display omitted] • The effects of nine common PFASs on IUGR risk were examined by single- and mixture-exposure method. • Maternal serum PFASs were positively associated with IUGR risk. • PFHpA (43.9%) was main contributors in the combined effect of PFASs on IUGR risk. [ABSTRACT FROM AUTHOR]

Previous studies have shown that per- and polyfluoroalkyl substances (PFAS) may have hepatotoxic effects in animals. However, epidemiological evidence in humans, especially pregnant women, is limited. This study aimed to assess the association of single and multiple PFAS exposure with serum markers of liver function in pregnant women. A total of 420 pregnant women from the Guangxi Zhuang Birth Cohort were enrolled from June 2015 to April 2019. Nine PFAS were measured in the maternal serum in early pregnancy. Data for liver function biomarkers, namely, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL), were obtained from medical records. In generalized linear model (GLM), there was a positive association of perfluorooctane sulfonate (PFOS) with ALT, perfluorodecanoic acid (PFDA) and perfluorobutanesulfonic acid (PFBS) with GGT, and perfluorohexane sulfonate (PFHxS) with TBIL and IBIL. In contrast, there was a negative association of perfluoroheptanoic acid (PFHpA) with TBIL. There were inverse U-shaped relationships of PFUnA with ALT and AST and PFDA with ALT by restricted cubic spline. The weighted quantile sum (WQS) regression model revealed the positive effects of the PFAS mixture on GGT, TBIL, DBIL, and IBIL. Bayesian kernel machine regression (BKMR) analysis confirmed that the PFAS mixture was positively associated with GGT, and PFBS was the main contributor. In addition, the BKMR model showed a positive association of individual PFBS with GGT, individual PFHxS with TBIL and IBIL, and a negative association of individual PFHpA with TBIL. Our findings provide evidence of an association between individual PFAS, PFAS mixture and maternal serum markers of liver function during pregnancy. Additionally, these findings also enhance concerns over PFAS exposure on maternal liver function and PFAS monitoring in pregnancy, reducing the effect of maternal liver dysfunction on maternal and infant health. [Display omitted] • Higher serum PFBS exposure is associated with higher GGT level. • Higher serum PFHxS is associated with higher TBIL and IBIL levels. • Higher serum PFHpA is associated with lower TBIL level. • The relationships of PFUnA with ALT and AST, and PFDA with ALT and GGT are nonlinear. • The joint effect of PFAS is positively associated with GGT, and PFBS is the main contributor. [ABSTRACT FROM AUTHOR]

Gestational anemia is a complication of pregnancy, and a low level of hemoglobin (Hb) has been linked to adverse pregnancy outcomes. Previous studies reported that PFASs were more strongly associated with Hb than red blood cells, indicating that Hb is more susceptible to the effect of PFASs. However, the evidences regarding the effects of per- and polyfluoroalkyl substances (PFASs) on gestational anemia are currently limited. Therefore, it is important to explore the effects of PFASs on anemia in Chinese pregnant women. A total of 821 pregnant women were recruited between June 2015 and April 2019 in the Guangxi Zhuang Birth Cohort. The concentrations of PFASs were assessed in maternal serum before 12 gestational weeks. To determine both individual and combined associations of PFASs exposure with anemia in the three stages of pregnancy, binary logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models were employed. In single-pollutant analysis, maternal exposure to perfluorododecanoic acid (PFDoA) and perfluoroheptanoic acid (PFHpA) were associated with anemia in the first trimester, exposure to PFHpA and perfluorobutanesulfonic acid (PFBS) were associated with anemia in the second trimester, and exposure to perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA) were associated with anemia in the third trimester. Notably, perfluoroundecanoic acid (PFUnA) had a nonlinear association with anemia in the third trimester. In multiple-pollutant analysis, a positive association of PFDoA with anemia in the first trimester and a negative association of PFBS with anemia in the second trimester were confirmed by BKMR. Exposure to PFASs mixture was not associated with anemia in all three trimesters. In WQS, there was a significantly negative association between the PFAS mixture and anemia in the second trimester. Maternal exposure to PFASs is associated with gestational anemia in different trimesters. [Display omitted] • Maternal exposure to PFDoA was related to a higher risk of gestational anemia in the first trimester. • Maternal exposure to PFBS was related to a lower risk of gestational anemia in the second trimester. • An inverted U-shaped relationship for PFUnA and gestational anemia in the third trimester. • There was no significant correlation between PFASs mixture and gestational anemia in all three trimesters. [ABSTRACT FROM AUTHOR]

Exposure to metals during pregnancy may affect maternal and infant health. However, studies on the combined effects of metals on the telomere length (TL) of newborns are limited. A prospective cohort study was conducted among 1313 mother–newborn pairs in the Guangxi Zhuang Birth Cohort. The concentrations of metals in maternal plasma during the first trimester were measured using inductively coupled plasma–mass spectrometry. We explored the associations between nine plasma metals and newborn TL using generalized linear models (GLMs), principal component analysis (PCA), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). The GLMs revealed the inverse association between plasma arsenic (percent change, −5.56%; 95% CI: -7.69%, −3.38%) and barium concentrations (−9.84%; 95% CI: -13.81%, −5.68%) and newborn TL. Lead levels were related to significant decreases in newborn TL only in females. The PCA revealed a negative association between the PC3 and newborn TL (−4.52%; 95% CI: -6.34%, −2.68%). In the BKMR, the joint effect of metals was negatively associated with newborn TL. Qgcomp indicated that each one-tertile increase in metal mixture levels was associated with shorter newborn TL (−9.39%; 95% CI: -14.32%, −4.18%). The single and joint effects of multiple metals were more pronounced among pregnant women carrying female fetuses and among pregnant women <28 years of age. The finding suggests that prenatal exposure to arsenic, barium, antimony, and lead and mixed metals may shorten newborn TLs. The relationship between metal exposures and newborn TL may exhibit heterogeneities according to infant sex and maternal age. [Display omitted] • Plasma arsenic and barium were negatively associated with newborn TL. • Plasma lead was negatively associated with newborn TL only in female infants. • The joint effects of metals were significantly negatively associated with newborn TL. • The overall effect of metals was more pronounced among female infants. • The overall effect of metals was more pronounced in pregnant women <28 years of age. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFASs) are persistent organic pollutants that may lead the adverse birth outcomes, including preterm birth (PTB). However, previous studies have reported inconsistent results on the association between PFASs and PTB, and lack of the epidemiological evidence regarding the effect of PFASs mixture on PTB. This study aimed to explore association of individual and multiple exposure to PFASs with PTB. The study subjects were consisted of 1341 pregnant women from Guangxi Zhuang Birth Cohort in Guangxi, China, from June 2015 to April 2019. Nine PFASs concentrations in the maternal serum were examined by ultrahigh liquid performance chromatography-tandem mass spectrometry, and the gestational weeks were obtained from medical records. We applied binary logistics regression model to explore correlation between individual PFAS and PTB and inspected the combined effect of PFASs mixture on PTB by applying Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression models. In adjusted logistics regression model, perfluorooctane sulfonate (PFOS), perfluoroheptanoic acid (PFHpA), perfluorobutanesulfonic acid (PFBS), ∑perfluorinated sulfonic acids (PFSA), and ∑PFASs were positively associated with the risk of PTB. In contrast, perfluoroundecanoic acid (PFUnA), perfluorohexane sulfonate (PFHxS), and perfluorooctanoic acid (PFOA) were negatively associated with the risk of PTB. These associations of n PFOS and PFHpA with PTB were found to be more pronounced in male infants. Restricted cubic splines (RCSs) showed an inverse U-shaped relationship between PFBS and PTB. Analysis from BKMR model showed a positive association between PFASs mixture and PTB, and no evidence of interactions among the nine PFASs were detected. Additionally, PFHpA, PFOS, and PFBS were identified as the main contributors for the effect of PFASs mixture on increasing the risk of PTB by BKMR and WQS models. Prenatal exposure to higher levels of PFASs mixture was associated with higher risk of PTB. [Display omitted] • Prenatal exposure to PFASs mixture was related to higher risk of PTB. • PFHpA(33.6%), PFOS(31.8%), and PFBS(18.9%) were main contributors in association with higher risk of PTB. • An inversely U-shaped relationship was observed between PFBS and PTB. • PFOS and PFHpA with PTB were sex-specific. [ABSTRACT FROM AUTHOR]

Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide, and it may be caused by environmental endocrine disruptors. Prenatal exposure to perfluoroalkyl substances (PFASs) in women has been linked to pregnancy disorders and adverse birth outcomes, but no data are available on the relationship between PFAS exposure during pregnancy and postpartum haemorrhage. This study aimed to explore the associations of maternal PFAS exposure with the postpartum haemorrhage risk and total blood loss. A total of 1496 mother-infant pairs in the Guangxi Zhuang birth cohort were included between June 2015 and May 2018. The concentration of PFASs in serum was detected using ultrahigh liquid chromatography-tandem mass spectrometry. Multiple binomial regression and linear regression models were used to analyse individual PFAS exposures. The mixture of PFASs was analysed using Bayesian Kernel Machine Regression (BKMR). In single substance exposure models, exposure to perfluorohexanesulfonic acid (PFHxS) increased the risk of postpartum haemorrhage (OR: 3.42, 95 % CI: 1.45, 8.07), while exposure to perfluorododecanoic acid (PFDoA) was inversely associated with the risk of postpartum haemorrhage (OR: 0.42, 95 % CI: 0.22, 0.80). The concentrations of perfluoroundecanoic acid (PFUnA) (β: 0.06, 95 % CI: 12.32, 108.82) and perfluorononanoic acid (PFNA) (β: 0.05, 95 % CI: 0.40, 88.95) exposure were positively correlated with the amount of postpartum haemorrhage; this result occurred only in the absence of covariate adjustment. In BKMR models, the risk of postpartum haemorrhage increased with increasing exposure to a PFAS mixture. In conclusion, our study suggested that maternal serum PFAS exposure during pregnancy was associated with the risk of postpartum haemorrhage. [Display omitted] • PFHxS were positively correlated with postpartum haemorrhage. • PFDoA were negatively correlated with postpartumhaemorrhage. • Exposure to a mixture of PFASs was positively correlated with postpartum haemorrhage. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB), a serious adverse birth outcome, is the leading cause of perinatal mortality and morbidity. Bisphenols induce endocrine disruption that spreads across the placenta, which may affect fetal growth and development. However, the effects of bisphenols on PTB, particularly their combined effects, remain unknown. This study investigated the association between prenatal bisphenol exposure and PTB. Study participants were 2023 mother-infant pairs that were selected from the Guangxi Zhuang Birth Cohort. Maternal serum bisphenol levels were measured using ultrahigh performance liquid chromatography-tandem mass spectrometry, and pregnancy outcomes were obtained from medical records. Multivariate logistic regression, restricted cubic spline, principal component analysis (PCA), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were used to examine the association between serum bisphenol levels and PTB. Ln-transformed BPA concentrations were associated with an increased risk of PTB only in female infants (OR = 1.30, 95% CI: 1.02, 1.64). Ln-transformed bisphenol F (BPF) concentrations were positively associated with the risk of PTB (OR = 1.73, 95% CI: 1.18, 2.55). Inverse U-shaped relationships were observed between bisphenol B (BPB), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) levels and the risk of PTB (P-overall < 0.05, P-non-linear < 0.05). After sex stratification, the association between BPA analogs and PTB was only observed in males. In Qgcomp analysis, bisphenol mixtures were related to an increased risk of PTB (OR = 1.52, 95% CI: 1.04, 2.21), with BPF (43.7%), BPS (29.6%) and BPA (26.8%) having the greatest positive contribution. Results indicate that prenatal exposure to bisphenol mixtures might increase the risk of PTB, which might be primarily driven by BPA, BPF and BPS. There may also be sex-specific and nonmonotonic dose-dependent effects. • The effects of bisphenol on PTB were examined by single- and mixture-exposure method. • Prenatal exposure to bisphenol mixtures might increase the risk of PTB. • There may be sex-specific and nonmonotonic dose-dependent effects. [ABSTRACT FROM AUTHOR]

Maternal environmental metal exposure is common, but long-term prospective epidemiological evidence of its impact on children's intellectual development is still insufficient. Data on maternal plasma metal levels and child intelligence were obtained for 211 3–6-year-old children from Guangxi Zhuang Birth Cohort. ICP-MS was employed to detect 17 metals, including 7 essential metals (Mn, Fe, Co, Ni, Cu, Zn, Mo) and 10 non-essential metals (As, Rb, Sr, Cd, Sb, Cs, Ba, W, Pb, U), in maternal plasma samples obtained before 13 weeks of gestation during the initial maternity checkup. Child intelligence was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. The GLM, RCS and mixture models were used to assess the associations of maternal plasma metal levels with child intelligence quotient (IQ) scores. The GLM analysis revealed that U had a significant adverse effect on child IQ scores in high-dose exposure groups (−9.236 [-18.644, −4.936], p = 0.006) after adjusting for covariates, while Sb showed a linear adverse effect on children's intelligence in the adjusted model (−4.028 [-7.432, −0.626], p = 0.021). BKMR modeling indicated that overall IQ scores decreased as concentrations of non-essential metals mixtures increased after adjusting for essential metal mixtures, consistent with findings from the WQS (β [95% CI], −8.463 [-14.449, −2.476], p = 0.007) and Qgcomp models (−7.003 [-12.928, −1.078], p = 0.022). Among the non-essential metals, U had the highest negative weight at 37.96%, followed by Pb (23.35%) and Sb (16.91%). Furthermore, potential interactions were observed between metals (Pb and U) and Sb in the study findings. Reducing exposure to non-essential metal mixtures, especially U, Sb and Pb, during early pregnancy and ensuring adequate intake of specific essential metal elements could be a critical intervention in addressing childhood intellectual impairment. [Display omitted] • Early pregnancy single Sb and U exposure was related to childhood IQ. • Non-essential metals mixture exposure in early pregnancy was associated with a risk of childhood IQ decline. • U (37.96%), Pb (23.35%) and Sb (16.91%) were the main contributors to the risk of childhood intelligence. • Essential metals intervene in the detrimental effects of non-essential metal mixtures on children's intelligence. [ABSTRACT FROM AUTHOR]

Bisphenols have endocrine-disrupting effects, which may disrupt hemoglobin (Hb) homeostasis and lead to anemia. However, the effects of bisphenols on anemia remain unknown. Therefore, we assessed the effects of single− and multiple−exposure to bisphenols on Hb levels and anemia of pregnant women. The study involved 2035 pregnant women from Guangxi Zhuang Birth Cohort in China. Generalized linear regression, principal component analysis (PCA), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were performed to examine the effects of serum bisphenols on Hb levels and the risk of anemia. After adjustment, elevated bisphenol A (BPA) levels were correlated with decreased Hb concentrations (β = −0.51; 95%CI: −0.92, −0.10) in the first trimester, and these correlations were more sensitive in mothers of males. Compared with the low-exposure group, bisphenol B (BPB) levels in the high-exposure group led to a 1.52 g/L (95%CI: −3.01, −0.03) decrease in Hb levels in the second trimester; tetrabromobisphenol A (TBBPA) levels in the high-exposure group led to a higher the risk of anemia in the third trimester (OR = 1.46; 95%CI: 1.07, 1.99); bisphenol F (BPF) in the high-exposure group led to lower Hb levels (β = −2.42; 95%CI:−4.69, −0.14) in mothers of male fetuses in the third trimester. Qgcomp showed that elevated levels of bisphenol mixture was correlated with (β = −1.42; 95%CI: −2.61, −0.24) decrease in Hb levels in the second trimester. PCA revealed a negative association between PC2 and Hb levels in the first trimester (β = −0.89; 95%CI: −1.61, −0.17). Similarly, a negative relationship was observed between PC1 and Hb levels in the third trimester among mothers with male fetuses (β = −1.00; 95%CI: −1.94, −0.06). Prenatal exposure to single and mixed bisphenols may decrease Hb levels and increase the risk of anemia during pregnancy, the associations may be greater in mothers with male fetuses than those with female fetuses. • The effects of bisphenols on Hb levels and anemia were examined in pregnant women. • Single- and multi-pollutant statistical approaches were performed. • Exposure to single and mixed bisphenols decreased Hb levels and elevated anemia risk. • The stronger effects were noted in mothers carrying male fetuses. [ABSTRACT FROM AUTHOR]

Previous epidemiological studies have examined the associations between exposure to perfluoroalkyl substances (PFASs) and the risk of hypertensive disorders of pregnancy (HDP). However, these studies have drawn discrepant conclusions and have some limitations. A nested case-control study was conducted with the Guangxi Zhuang Birth Cohort (GZBC), a prospective, ongoing birth cohort that was implemented in Guangxi, China, in June 2015. Maternal serum concentrations of nine PFASs were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The associations between PFAS exposure and the risk of HDP were assessed using logistic regression (single-exposure), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. A total of 136 HDP cases and 408 controls were enrolled in this study. In logistic regression models, perfluoroundecanoic acid (PFUnA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorobutanesulfonic acid (PFBS) were positively associated with HDP, while perfluorohexane sulfonate (PFHxS) was inversely associated with HDP. In the BKMR analysis, the joint effect of PFASs was positively associated with HDP. PFOS and PFBS showed positive trends, while PFHxS and PFHpA showed inverse trends. In WQS regression analysis, we calculated two WQS indices that were estimated using constraints in both the positive and negative directions of effects. Both WQS indices were significantly associated with HDP (OR: 2.663, 95% CI: 1.795–3.951; OR: 0.338, 95% CI: 0.229–0.499, respectively). PFBS, PFOS and PFUnA had significant weights in the positive effect direction; PFHxS, perfluoroheptanoic acid (PFHpA) and perfluorododecanoic acid (PFDoA) had significant weights in the negative effect direction. Considering all model results, we found that combined exposure to nine PFASs had a positive effect on the development of HDP. Moreover, PFOS and PFBS were positively associated with the HDP risk, while PFHxS and PFHpA were negatively associated with the HDP risk in women in Guangxi, China. [Display omitted] • A nested case-control study was conducted. • Logistic regression, BKMR model and WQS regression model. • The joint effect of PFASs was significantly positively associated with HDP. • PFOS and PFBS were positively associated with the risk of HDP. • PFHxS and PFHpA were negatively associated with the risk of HDP. [ABSTRACT FROM AUTHOR]