Placental weight mediates association between prenatal exposure to cooking oil fumes and preterm birth.

Background: There are some reports on association between maternal prenatal cooking oil fume (COF) exposure and preterm birth (PTB), but its mechanism remains poorly understood. Therefore, this study aims to assess whether placental weight mediates their associations.Method: We enrolled 619 pregnant women delivering PTB newborns as cases and 1701 delivering full-term appropriate for gestational age newborns as controls. They were inquired with a self-reported questionnaire about prenatal COF exposure, socio-demographics and obstetric characteristics at Women and Children's Hospitals of Shenzhen and Foshan. After controlling for the potential confounders, a series of logistic and linear regressions were conducted to assess associations among COF exposure, placental weight and PTB, and the mediation of placental weight in the association between COF exposure and PTB.Results: Maternal prenatal COF exposure was significantly associated with PTB and the frequency of prenatal COF exposure was negatively associated with placental weight. Compared with mother who never cooked, those cooking occasionally, sometimes or often increased the risk of PTB, and similarly, those cooking between half to an hour was also showed a higher risk of PTB. Typical Chinese cooking methods including stir-frying, pan-frying and deep-frying were also associated with PTB. Different oil types mainly used, including peanut oil, corn oil and animal oil were associated with PTB as well. Mediation analysis illustrated that placental weight partially mediated 13.60% (95% CI = 10.62-33.20%) of the effects on the association between the frequency of maternal prenatal COF exposure and PTB.Conclusion: Maternal cooking during pregnancy and the frequency of prenatal COF exposure might increase the risk of PTB, in which placenta might play mediation role.

Appetite during the second and third trimesters mediates the impact of prenatal environmental tobacco smoke exposure on symmetric full-term low birth weight.

Objective: To examine the relationship of prenatal environmental tobacco smoke (ETS) exposure and full-term low birth weight (FT-LBW) when taking anthropometric proportionality into consideration, and explore whether appetite mediates their association.Study design: We conducted a case-control study among pregnant women at two Women and Children's Hospitals in Guangdong, China. Information was collected through interview and medical records review. A series of logistic and linear regressions were used to examine the relationships of prenatal ETS exposure, appetite, and FT-LBW.Results: After adjusting for the potential confounders, prenatal ETS exposure was significantly negatively associated with FT-LBW (OR: 1.83, 95%CI: 1.35-2.48) and negatively correlated with maternal appetite in second and third trimester during pregnancy (ß: -0.11, standard error: 0.03). Moreover, mediation analysis illustrated that maternal appetite partially mediated 12.00% of their relationship. However, subgroup analysis showed that prenatal ETS exposure was linked to higher risk of symmetric FT-LBW (OR: 2.26, 95%CI: 1.56-3.26) but not asymmetric FT-LBW. And maternal appetite explained only 6.45% of their relationship.Conclusions: Maternal prenatal ETS exposure increased risk of having symmetric FT-LBW infant, and appetite might mediate their relationship partially. This study emphasizes the importance of sample homogeneity and stresses the needs to improve the public awareness of the harmful effects of ETS.

Age-specific reference values for cerebrospinal fluid protein concentrations in children in southern China.

Cerebrospinal fluid (CSF) protein values decline over the first few months of life as the infant's blood-CSF barrier matures. However, published studies have not reported CSF protein reference values of Chinese infants and differ in the reported rate, timing, and magnitude of this decline. The objective of this study was to determine reference intervals for CSF protein using available data of children in southern China. This retrospective study included infants who had a lumbar puncture (LP) performed in the Department of Pediatrics of Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan of an urban tertiary care children's hospital between January 1, 2008 and May 31, 2018. Infants with conditions suspected or known to cause elevated CSF protein concentrations were excluded. Of 3712 infants undergoing LP, 1043 (28.1%) met inclusion criteria. Results showed that there is an age-related decline in CSF protein concentration. The median CSF protein value was 62 mg/dL [interquartile range (IQR): 47-81 mg/dL] in infants aged 0 to 56 days (group 1). The 95th percentile values were 116 mg/dL for infants 0 to 28 days and 80 mg/dL for infants 29 to 56 days. The 95th percentile values by age category were as follows: ages 0 to 14 days, 117 mg/dL; ages 15 to 28 days, 107 mg/dL; ages 29 to 42 days, 96 mg/dL; and ages 43 to 56 days, 74 mg/dL. The median CSF protein value was 21 mg/dL (IQR: 16-31 mg/dL) in infants aged 2 months to <3 years (group 2). The 95th percentile values were 57 mg/dL for infants 2 to <6 months and 34 mg/dL for infants 6 to ≤24 months. The 95th percentile values by age category were as follows: ages 2 to <3 months, 66 mg/dL; ages 3 to <4 months, 52 mg/dL; ages 4 to <5 months, 53 mg/dL; and ages 5 to <6 months, 42 mg/dL. We quantify the age-related decline in CSF protein concentrations among infants 2 years of age and younger and provide age-specific reference values. The values reported here can be used to interpret the results of LP in infants ≤2 years of age.

Maternal exercise during pregnancy reduces the risk of preterm birth through the mediating role of placenta.

OBJECTIVE: The extent of research on maternal exercise during pregnancy and the risk of preterm birth (PTB) have grown substantially, but conclusions still remained controversial. Thus, this study aims to examine the relationship of maternal exercise during pregnancy and PTB and explore whether placenta mediates their relationship. STUDY DESIGN: We investigated 849 pregnant women delivering PTB newborns (cases) and 1306 delivering full-term appropriate for gestational age newborns (controls) in this case-control study. Information concerning maternal exercise during pregnancy, sociodemographics and obstetric characteristics were collected at Women and Children's Hospitals of Shenzhen and Foshan in Guangdong, China. A series of logistic and linear regressions were used to examine the relationships of maternal exercise during pregnancy, placenta, and PTB. RESULTS: After adjusting for the potential confounders, maternal exercise frequency and duration during pregnancy were negatively associated with PTB. Moreover, compared with mother taking no exercise during pregnancy, those taking exercise lowered the risk of PTB except those taking low/medium frequency and short duration exercise, and their adjusted ORs ranged from 0.43 to 0.65. Furthermore, mediation analysis illustrated that placental weight partially mediated 65.20% of the effects of maternal exercise frequency on PTB, as well as 41.98% of the association between maternal exercise duration and PTB. CONCLUSIONS: Maternal exercise during pregnancy is beneficial for lowering the risk of PTB, especially when taking appropriate and enough exercise. Placenta weight may partially mediate the association between maternal exercise during pregnancy and PTB.

Gene-gene-environment interactions of prenatal exposed to environmental tobacco smoke, CYP1A1 and GSTs polymorphisms on full-term low birth weight: relationship of maternal passive smoking, gene polymorphisms, and FT-LBW.

OBJECTIVE: To examine the interaction effects of prenatal exposed to environmental tobacco smoke (ETS) and genotypes of cytochrome P4501A1 (CYP1A1), glutathione S-transferases (GSTs) on the risk of full-term low birth weight (FT-LBW). STUDY DESIGN: We conducted a case-control study among pregnant women at two Women and Children's Hospitals in Guangdong, China (n = 910). Information was collected through interview, medical records review, and blood lab tests. Maternal selfreport and serum cotinine concentration were combined to define prenatal exposed to ETS. Logistic regression approach was applied for statistical analysis. RESULTS: Our results showed that regardless of genotypes, prenatal exposed to ETS significantly increased the risk of FT-LBW. Then, two-way interactions showed increased prevalence of FT-LBW in prenatal exposed to ETS mothers with the CYP1A1 variant genotype (MspI "CC"), or with GSTT1-null genotype. Furthermore, three-way interactions showed that women with CYP1A1 variant (MspI "TC" or BsrDI "AG") genotypes and GSTT1 "null" genotype had higher risk to give birth of FT-LBW. Additionally, among nonexposed ETS mothers, genotype did not independently confer adverse effects on FT-LBW. CONCLUSIONS: Our results revealed that prenatal exposed to ETS is independently associated with FT-LBW while gene polymorphisms of CYP1A1 and GSTs merely play modified roles in this process. This study extends understanding of three-way interaction, and stresses the need to tobacco control toward pregnant women for better pregnant outcomes.

Association between prenatal exposure to cooking oil fumes and full-term low birth weight is mediated by placental weight.

OBJECTIVE: Evidence regarding the association between prenatal exposure to cooking oil fumes (COF) and full-term low birth weight (FTLBW) is still controversial, and the mechanism remains unclear. This study thus aims to explore the association of prenatal COF exposure with off-spring FT-LBW as well as the mediating role of placenta in their association. METHODS: A case-control study enrolling 266 pregnant women delivering FTLBW newborns (cases) and 1420 delivering normal birth weight (NBW) newborns (controls) was conducted. Information on prenatal COF exposure, socio-demographics, and obstetric conditions were collected at the Women's and Children's Hospitals of Shenzhen and Foshan in Guangdong, China. Linear and hierarchical logistic regression models were undertaken to explore the associations among COF exposure, placenta and birth weight, as well as the mediation effect of placental weight. RESULTS: After controlling for potential confounders, prenatal COF exposure was significantly associated with the higher risk of FT-LBW (OR = 1.31, 95% CI= 1.06-1.63) and the lower placental weight (ß = -0.12, 95% CI= -0.23 ~ -0.005). Compared with mothers who never cooked, those cooking sometimes (OR= 2.99, 95% CI= 1.48-6.04) or often (OR= 3.41, 95% CI= 1.40-8.34) showed a higher risk of FT-LBW, and likewise, those cooking for less than half an hour (OR= 2.08, 95% CI= 1.14-3.79) or cooking between half to an hour (OR= 2.48, 95% CI= 1.44-4.29) were also more likely to exhibit FT-LBW. Different cooking methods including pan-frying (OR= 2.24, 95% CI= 1.30-3.85) or deep-frying (OR= 1.78, 95% CI= 1.12-2.85) during pregnancy were associated with increased FT-LBW risks as well. The further mediation analysis illustrated that placental weight mediated 15.96% (95% CI: 12.81~28.80%) and 15.90% (95% CI= 14.62%~16.66%) of the associations of cooking during pregnancy and frequency of prenatal COF exposure, respectively, with FT-LBW.

Mediating role of maternal serum interleukin-1beta and tumor necrosis factor-alpha in the association between environmental tobacco smoke exposure in pregnancy and low birth weight at term.

OBJECTIVES: To explore the mediation effects of maternal serum interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) on the association between environmental tobacco smoke (ETS) exposure during pregnancy and low birth weight (LBW) at term. METHODS: ETS exposure, birth weight, blood sample and covariates were collected from 195 pregnant women delivered term LBW infants and 195 controls delivered normal birth weight infants in two Maternity and Child Hospitals in Guangdong, China. Maternal serum IL-1ß and TNF-α were measured by flow cytometry. Logistic regression models and path analyses explored the mediation effects of maternal IL-1ß and TNF-α on the association between ETS exposure and LBW. RESULTS: LBW was significantly associated with maternal ETS exposure (OR = 2.14 (95% CI =1.06-4.32)). TNF-α and IL-1ß were significantly associated with both LBW (OR = 1.87 (1.41-2.47) and OR = 1.53 (1.14-2.05)) and ETS (ß = 0.32 (0.04-0.60) and ß = 0.27 (0.05-0.49)). Traditional mediation analyses indicated the separate mediation effect of TNF-α and IL-1ß was 32.2% and 24.6%, respectively. Path analysis revealed the combined mediation effects of TNF-α and IL-1ß as 29.4% in the pathway from ETS exposure to LBW. CONCLUSIONS: Maternal serum IL-1ß and TNF-α may play a mediating role in the association between maternal ETS exposure during pregnancy and term LBW.

The mediating role of placenta in the relationship between maternal exercise during pregnancy and full-term low birth weight.

OBJECTIVE: To explore the association of maternal exercise during pregnancy with full-term low birth weight (FT-LBW) and whether placenta mediates their association. STUDY DESIGN: We investigated 326 pregnant women delivering FT-LBW weight newborns (cases) and 1644 delivering full-term normal birth weight newborns (controls) in this case-control study. Information concerning maternal exercise during pregnancy, socio-demographics and obstetric characteristics were collected at Women and Children's Hospitals of Shenzhen and Foshan in Guangdong, China. RESULTS: After adjusting for the potential confounders, maternal exercise frequency and duration during pregnancy were significantly negatively associated with FT-LBW, respectively. Moreover, compared with mothers taking no exercise during pregnancy, those taking exercises were significantly negatively associated with FT-LBW except those taking low/medium frequency and short duration exercise and high-frequency and long duration exercise, and their adjusted ORs ranged from 0.30 to 0.62. Furthermore, mediation analysis illustrated that placental weight partially mediated 27.20% of the association between maternal exercise frequency during pregnancy and FT-LBW, but not the association between maternal exercise duration during pregnancy and FT-LBW. CONCLUSIONS: Maternal exercise during pregnancy is beneficial for lowering FT-LBW risk, especially when taking appropriate and enough exercise. Placenta weight partially mediates the association between maternal exercise frequency during pregnancy and FT-LBW.

Potential pathways by which maternal second-hand smoke exposure during pregnancy causes full-term low birth weight.

It is well documented that maternal exposure to second-hand smoke (SHS) during pregnancy causes low birth weight (LBW), but its mechanism remains unknown. This study explored the potential pathways. We enrolled 195 pregnant women who delivered full-term LBW newborns, and 195 who delivered full-term normal birth weight newborns as the controls. After controlling for maternal age, education level, family income, pre-pregnant body mass index, newborn gender and gestational age, logistic regression analysis revealed that LBW was significantly and positively associated with maternal exposure to SHS during pregnancy, lower placental weight, TNF-α and IL-1ß, and that SHS exposure was significantly associated with lower placental weight, TNF-α and IL-1ß. Structural equation modelling identified two plausible pathways by which maternal exposure to SHS during pregnancy might cause LBW. First, SHS exposure induced the elevation of TNF-α, which might directly increase the risk of LBW by transmission across the placenta. Second, SHS exposure first increased maternal secretion of IL-1ß and TNF-α, which then triggered the secretion of VCAM-1; both TNF-α and VCAM-1 were significantly associated with lower placental weight, thus increasing the risk of LBW. In conclusion, maternal exposure to SHS during pregnancy may lead to LBW through the potential pathways of maternal inflammation and lower placental weight.

Combinations of CYP2A6*4 and Glutathione S-Transferases Gene Polymorphisms Modify the Association Between Maternal Secondhand Smoke Exposure During Pregnancy and Small-for-Gestational-Age.

INTRODUCTION: Risk of small-for-gestational-age (SGA) birth varied considerably in women exposed to secondhand smoke (SHS) during pregnancy. We examined whether this variation was explained by mothers' one Phase I (CYP2A6*4, activation of tobacco toxics) and two Phase II (GSTM1 and GSTT1, detoxification) metabolic genotypes. METHODS: We enrolled 468 Chinese pregnant women (115 delivering SGA and 353 delivering non-SGA newborns) shortly before delivery. SHS exposure during pregnancy was defined as self-reported daily exposure time being more than 0 minute. We fitted multivariable logistic regression models to examine whether CYP2A6*4, GSTM1, and GSTT1 gene polymorphsims and their combinations modified the association between SHS exposure and SGA. RESULTS: In the total sample, more mothers of SGA newborns were exposed to SHS during pregnancy than mothers of non-SGA newborns (38.3% vs. 31.4%). CYP2A6*4, GSTM1, and GSTT1 genes alone could not modify the association between SHS exposure and SGA. The combination of CYP2A6*4 and GSTT1 high-risk genotypes (CYP2A6*1/*1 and GSTT1-absent [high-risk] vs. other combinations as a whole [low-risk]) significantly (P value, .045) modified the association between SHS exposure and SGA. Among mothers with high-risk genotypes, SHS during pregnancy was significantly associated with SGA (confounder-adjusted odds ratio, 2.31 [95% confidence interval, 1.20-4.42]). Among mothers with low-risk genotypes, however, SHS exposure during pregnancy was not associated with SGA (1.14 [0.64-2.04]). CONCLUSIONS: Chinese pregnant women with the combination of CYP2A6*1/*1 and GSTT1-absent genotypes are at particularly high-risk of SHS-related SGA.

Comparison of secondhand smoke exposure measures during pregnancy in the development of a clinical prediction model for small-for-gestational-age among non-smoking Chinese pregnant women.

OBJECTIVE: To compare predictive values of small-for-gestational-age (SGA) by different measures for secondhand smoke (SHS) exposure during pregnancy and to develop and validate a prediction model for SGA using SHS exposure along with sociodemographic and pregnancy factors. METHODS: We compared the predictability of different measures of SHS exposure during pregnancy for SGA among 545 Chinese pregnant women, and then used the optimal SHS measure along with other clinically available factors to develop and validate a prediction model for SGA. We fit logistic regression models to predict SGA by single measures of SHS exposure (self-report, serum cotinine and CYP2A6*4) and different combinations (self-report+cotinine, cotinine+CYP2A6*4, self-report+CYP2A6*4 and self-report+cotinine+CYP2A6*4). RESULTS: We found that self-reported SHS exposure alone predicted SGA (area under the receiver operating characteristic curve or area under the receiver operating curve (AUROC), 0.578) better than the other two single measures (cotinine, 0.547; CYP2A6*4, 0.529) or as accurately as combined SHS measures (0.545-0.584). The final prediction model that contained self-reported SHS exposure, prepregnancy body mass index, gestational weight gain velocity during the second and third trimesters, gestational diabetes, gestational hypertension and the third-trimester biparietal diameter Z-score could predict SGA fairly accurately (AUROC, 0.698). CONCLUSIONS: Self-reported SHS exposure at peribirth performs better in predicting SGA than a single measure of serum cotinine at the same time, although repeated biochemical cotinine assessments throughout pregnancy may be optimal. Our simple prediction model is fairly accurate and can be potentially used in routine prenatal care.

Influence of CYP2A6*4 genotypes on maternal serum cotinine among Chinese nonsmoking pregnant women.

INTRODUCTION: Serum cotinine is a common biomarker for smoking and secondhand smoke (SHS) exposure, but it can be affected by the activity of nicotine-metabolizing enzymes. This study investigated the influence of CYP2A6*4 genotypes on serum cotinine among nonsmoking pregnant women. METHODS: We analyzed the data from 545 Chinese nonsmoking pregnant women in a case-control study on SHS exposure and birth outcomes in southern China. Participants self-reported their status and duration of SHS exposure during pregnancy right after delivery in hospital. Research staff used polymerase chain reaction to genotype CYP2A6*4 and enzyme-linked immunosorbent assay to measure cotinine levels in maternal serum samples collected before delivery. We stratified women by their self-reported SHS exposure status and CYP2A6*4 genotypes and then compared their median levels of serum cotinine. RESULTS: Among women who self-reported non-SHS exposure (n = 317), the median serum cotinine levels were 2.83ng/ml for those with CYP2A6*1/*1 genotype, 1.39ng/ml for CYP2A6*1/*4, and 0.77ng/ml for CYP2A6*4/*4, respectively. Among women who self-reported SHS exposure (n = 228), the median cotinine levels were 3.32ng/ml for those with CYP2A6*1/*1 genotype, 2.38ng/ml for CYP2A6*1/*4, and 1.56ng/ml for CYP2A6*4/*4, respectively. Strikingly, self-reported SHS-exposed women with CYP2A6*1/*4 or CYP2A6*4/*4 genotype had significantly lower (rather than higher) median cotinine levels than self-reported non-SHS-exposed women with CYP2A6*1/*1 genotype (p = .012). CONCLUSIONS: CYP2A6*4 genotype is associated with lower serum cotinine among Chinese nonsmoking pregnant women. Measuring CYP2A6*4 genotype may help to improve the validity of SHS exposure measurement by serum cotinine in pregnant women and possibly also in other nonpregnant populations.

Interaction between maternal passive smoking during pregnancy and CYP1A1 and GSTs polymorphisms on spontaneous preterm delivery.

OBJECTIVE: The present study aimed to examine the association between maternal passive smoking during pregnancy and the risk of spontaneous PTD and to explore the potential interaction of the single or joint gene polymorphism of CYP1A1 and GSTs with maternal passive smoking on the risk of spontaneous PTD. METHOD: We investigated whether the association between maternal passive smoking and PTD can be modified by 2 metabolic genes, i.e. cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs), in a case-control study with 198 spontaneous preterm and 524 term deliveries in Shenzhen and Foshan, China. We used logistic regression to test gene-passive smoking interaction, adjusting for maternal socio-demographics and prepregnancy body mass index. RESULTS: Overall, maternal passive smoking during pregnancy was associated with higher risk of PTD (adjusted odds ratio = 2.20 [95% confidence interval: 1.56-3.12]). This association was modified by CYP1A1 and GSTs together, but not by any single genotype. For cross-categories of CYP1A1 Msp I and GSTs, maternal passive smoking was associated with higher risk of PTD among those women with CYP1A1 "TC/CC"+ GSTs "null", but not among women with other genotypes; and this interaction was significant (OR = 2.66 [95% CI: 1.19-5.97]; P-value: 0.017). For cross-categories of CYP1A1 BsrD I and GSTs, maternal passive smoking was associated with higher risk of PTD only among those women with CYP1A1"AG/GG"+ GSTs "null", but not among women with other genotypes; and this interaction was significant (OR = 3.00 [95% CI: 1.17-7.74]; P-value: 0.023). CONCLUSIONS: Our findings suggest that the combined genotypes of CYP1A1 and GSTs can help to identify vulnerable pregnant women who are subject to high risk of spontaneous PTD due to passive smoking.