Early prenatal exposure to air pollutants and congenital heart disease: a nested case-control study

BACKGROUND@#Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease.@*METHODS@#The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease.@*RESULTS@#A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m3 increase of gestational exposure to PM2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1st-2nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O3 exposure during the 1st week and SO2 exposure during 6th-7th weeks in the first trimester, while no significant findings for other air pollutants.@*CONCLUSIONS@#This study highlighted that gestational exposure to PM2.5, O3, and SO2 had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.

Effects of subclinical hypothyroidism during pregnancy treated with LT 4 on the growth and neuropsychology of offspring aged 0-36 months: A cohort study / 中华内分泌代谢杂志

Objective:To evaluate the effects of subclinical hypothyroidism during pregnancy treated with LT 4 on the growth and neuropsychology of offspring aged 0-36 months. Methods:A maternal-infant cohort was established in healthy singleton pregnant women aged 20-45 years without history of thyroid disease. Women developing subclinical hypothyroidism during pregnancy were treated with LT4. The weight, length, and head circumference of the offspring were recorded between 0 to 36 months after birth. Meanwhile, infant nutrition and family support were investigated. The Neuropsychological Development Questionnaire of 0-6 year old children was used to evaluate the neurodevelopment of offspring.Results:A total of 186 mother-infant pairs were included. All subjects were divided into the euthyroidism(ETH) group( n=136) and subclinical hypothyroidism(SHT) group( n=50) according to maternal thyroid function during pregnancy. The Z-scores(adjusted by months of age and gender) of weight, length, weight/length at birth, weight/length at 1 month, head circumference at 6 months, length at 8 months, weight/length at 24 months of SHT group were lower than those of the ETH group( P<0.05). Furthermore, the language competence of the SHT offspring at 12 months of age was also lower than that of the ETH group( P<0.05). Maternal subclinical hypothyroidism treated with LT 4 did not significantly affect preterm delivery, low birth weight, and developmental quotient <85, but reduced the risk of macrosomia(AOR 0.206, 95% CI 0.046-0.929, P=0.040). Conclusion:Although women with subclinical hypothyroidism received LT 4 treatment during pregnancy, the offspring still may suffer adverse effects on their growth and neural development.

Screening results and analysis of risk factors of developmental dysplasia of hip in infants in Tianjin / 中华骨科杂志

Objective:To investigate the Graf classification results and risk factors of infants for developmental dysplasia of the hip (DDH) by B-ultrasound screening in Tianjin.Methods:A retrospective analysis was conducted from January 2013 to December 2020 using the three-tier maternal and child health care management and the Tianjin maternal and child health information system for the early B-ultrasound screening data of 6-8 weeks old infants. The "2+1" screening model of "primary screening-re-screening-diagnostic treatment" was applied. The positive screening rate and age of infants at the time of referral for treatment in different years and different Graf classifications were analyzed, and the differences in positive infants with different sex, parity, fetal position, mode of production, gestational age, birth weight, and family history were compared. Binary logistic regression was used to analyze risk factors for DDH.Results:A total of 807 889 babies were screened, and 2 039 children (2 841 hips) were detected with B-ultrasound Graf classification count IIa and above, with the positive rate was 2.52‰ (2 039/807 889). Among the abnormal hips, 685 were type IIa(+) hips, 959 were type IIa(-) hips, 367 were type IIb hips, 262 were type IIc hips, 227 were type D hips, 265 were type III hips, and 76 were type IV hips. Type IIa(-) was the most common, accounting for 33.76% (959/2 841), type IIa(+) accounted for 24.11% (685/2 841), type D and above was 19.99%(568/2 841). The abnormality rate of the left hip was 2.02‰ (1 632/807 889), which was greater than 1.50‰ (1 209/807 889) of the right side, and the difference is statistically significant (χ 2=63.09, P<0.001). The rate of hip abnormalities in female infants was 3.27‰ (2 541/777 272), greater than 0.36‰ (300/838 506) in male infants, which the difference between the sexes had statistically significant (χ 2=1 947.871, P<0.001). The positive rate of DDH in male infants was 0.50‰ (209/419 253), and that in female infants was 4.71‰ (1 830/388 636). The detection ratio of male to female infants was 1∶8.76, and the difference in the positive rate of DDH between the sexes was statistically significant (χ 2=1 420.102, P<0.001). Different fetal position (cephalic position/breech presentation), delivery method (normal delivery/cesarean section), birth weight (normal/low weight), family history (with DDH/without DDH) showed statistically significant differences in the positive rate of DDH ( P<0.05), whereas there was no significant difference in the positive rate of DDH at different parity (first/second and above) and gestational age (term/premature) ( P>0.05). Logistic regression analysis showed that gender ( OR=10.50, P<0.001) and fetal position ( OR=3.40, P<0.001) were independent risk factors for DDH, and gestational age ( OR=0.91, P<0.001) was a protective factor for DDH. Differences in referral age of infants with different B-ultrasound Graf classification from year to year were statistically significant ( P<0.05). Conclusion:Through the "2+1" screening model of "primary screening-re-screening-diagnostic treatment", the DDH positive rate in 6-8 weeks old infants in Tianjin was 2.52‰, and the positive rate of DDH in female infants and left hip was higher. The more severe the Graf classification of B-ultrasound was, the younger the age of referral was. Women and infants with breech presentation had a higher risk of developing DDH, and the risk of DDH in preterm infants was lower.

Study of association between bile acid metabolites in early pregnancy and overweight / 中华内分泌代谢杂志

Objective:This study examined the associations between the levels of bile acids in early pregnancy and the occurrence of overweight.Methods:From 2010 to 2012, 22 302 pregnant women were recruited by Tianjin Women and Children′s Health Center to investigate gestational diabetes. Two hundred and forty-three women with gestational diabetes mellitus provided overnight fasting blood samples in the first trimester, and 243 counterparts without gestational diabetes mellitus matched on age were selected randomly to establish a nested case-control study. The association between bile acids and overweight were evaluated by binary logistic regression with data from 166 overweight pregnant women (body mass index≥24.0 kg/m 2) and 320 normal weight subjects (body mass index <24.0 kg/m 2). Results:Compared to non-overweight group, the level of primary unconjugated bile acids in overweight group was significantly higher. After adjustment of confounding factors, the OR of cholic acid (CA)>0.086 nmol/mL for overweight was 2.09 (95% CI 1.14-3.80, adjusted P=0.040), and OR of chenodeoxycholic acid (CDCA)>0.043 nmol/mL was 2.15 (95% CI 1.22-3.78, adjusted P=0.040) compared with the lower groups. However, the significant associations between the other bile acids and overweight were not detected. Stepwise selection was used to identify significant bile acid species in logistic regression. We found that only CA was independently associated with overweight, and the OR of CA>0.086 nmol/mL vs≤0.086 nmol/mL was 2.03 (95% CI 1.11-3.74, P=0.022). Conclusion:CA and CDCA in early pregnancy maybe associated with overweight, and CA might be independently associated with overweight.

Effects of iodine nutrition during pregnancy and lactation on postpartum thyroid function in women with subclinical hypothyroidism / 中华内分泌代谢杂志

Objective To evaluate the effects of maternal iodine nutrition levels on postpartum thyroid function, and to provide clinical evidence for accurate iodine supplementation in women with subclinical hypothyroidism during pregnancy. Methods This study collected single-pregnant women who had no history of thyroid diseases before pregnancy in our city. Thyroid function and urinary iodine results were continuously recorded during pregnancy and lactation. All subjects were divided into subclinical hypothyroidism group and euthyroidism group according to their thyroid function during pregnancy. The relationship between urinary iodine levels during pregnancy and lactation with postpartum thyroid function were analyzed. Results A total of 148 maternal women were collected, including 41 cases of subclinical hypothyroidism group and 107 cases of euthyroidism group. The urinary iodine level in pregnant women was higher than that in lactation ( median 174.75 vs 149.89μg/L, P<0.05) . However, the iodine deficiency ratio(23.6％) during pregnancy was higher than that during lactation (5.4％). There were significant differences in the change of urinary iodine in each time interval during pregnancy and lactation ( P<0.05). A total of 56 maternal women developed postpartum thyroiditis ( PPT). The incidence of PPT in pregnant women with TPOAb-positive in early pregnancy was higher than that in TPOAb-negative patients (χ2=10.811, P=0.001) . The urinary iodine concentration in the 12-month postpartum period was lower in women with PPT than that in womenwithoutPPT(P<0.05).Coxregressionanalysisshowedthatiodinedeficiencyduringlactation(HR=3.870, 95％CI 1.595-9.392, P=0.003) and TPOAb positive in early pregnancy (HR=3.679, 95％ CI 1.466-9.233, P<0.05) increased the risk of PPT. Subgroup analysis also showed a similar risk increase of PPT in women with hypothyroidism during pregnancy (HR=8.318, 95％CI 2.383-29.029, P<0.05). However, this association was not found in euthyroidism group. Conclusion The urinary iodine level of women during pregnancy and lactation in our iodine suitable areas is within normal range, but attention should still be paid to the effect of iodine deficiency on breast-feeding women, especially among those with subclinical hypothyroidism.

Associations of urinary iodine and blood selenium levels with subclinical hypothyroidism and thyroid antibodies during the first half pregnancy in Tianjin women / 中华内分泌代谢杂志

Objective To investigate the associations of urinary iodine concentration ( UIC) and blood selenium levels with subclinical hypothyroidism and thyroid antibodies during the first half pregnancy in women. Methods A total of 239 pregnant women(7-20 weeks)were selected. The baseline data were collected, and serum TSH, FT4 , thyroid peroxidase antibody ( TPOAb), thyroglobulin antibody ( TgAb), blood selenium, and urinary iodine concentration(UIC) levels were measured. Results The median level of urinary iodine among 239 women was 156. 96 μg/ L. The distributions of pregnant women with iodine deficiency, iodine adequate, more-than-adequate or excessive iodine intake were 43. 9％ , 38. 9％ , 17. 2％ , respectively. The percentage of more-than-adequate and excessive iodine in women with subclinical hypothyroidism was higher than that in women with euthyroidism. The serum TSH level in women with UIC≥250 μg/ L was higher than those with 150≤UIC<250 μg/ L and UIC<150 μg/ L (P<0. 05). The serum TSH level in women with blood selenium<95 μg/ L was higher than those with selenium≥95μg/ L(P<0. 05). Logistic regression analysis showed that the risk of subclinical hypothyroidism in women with UIC≥250 μg/ L was increased by 3. 498 fold(95％ CI 1. 588-7. 704)as compared with those with 150≤UIC<250 μg/ L. The risk of subclinical hypothyroidism in women with blood selenium <80 μg/ L was increased by 2. 667 fold (95％ CI 1. 123-6. 331) compared with those with 90 ≤ selenium < 100 μg/ L. After adjusting for age, gestational weeks, residential district, TPOAb, TgAb, taking compound nutritional supplements, more-than-adequate and excessive iodine still increased the risk of subclinical hypothyroidism(OR= 3. 014, 95％ CI 1. 310-6. 938). Women with UIC≥250 μg/ L and blood selenium <95 μg/ L revealed the increased risk of subclinical hypothyroidism as compared to those with 150≤UIC<250 μg/ L and selenium≥95 μg/ L(OR=5. 429, 95％ CI 1. 929-15. 281). After adjusting for age, gestational weeks, residential district, TPOAb, TgAb, taking compound nutritional supplements, the fingdings still existed. Conclusion The nutrient condition of iodine and selenium of the pregnant women in Tianjin during the first half pregnancy should be noticed. The individualized supplement of iodine and selenium, if needed, should be performed to decrease the risk of subclinical hypothyroidism.

The relationship of the folate metabolism related gene polymorphisms of MTHFR and MTRR with unexplained recurrent spontaneous abortion / 天津医药

Objectives To investigate the relationship of methylenetetrahydrofolate reductase (MTHFR) and methioninesynthase reductase (MTRR) with unexplained recurrent spontaneous abortion (URSA). Methods Case control study was used to select 244 patients with URSA (miscarriage group) and 116 normal women (control group) who were admitted to Tianjin Medical University General Hospital and Tianjin Women’s and Children’s Health Center from January 2013 to March 2015. The oral mucosal epithelial cells were extracted using fluorescence quantitative PCR to detect MTHFR gene C677T, A1298C and MTRR gene loci of A66G single nucleotide polymorphisms (SNP). The relationship between folate metabolism related gene polymorphisms of MTHFR and MTRR and URSA was analysed. Results The frequency of C677T genotype MTHFR was significantly higher in URSA group than that in the control group, and the frequency of CT genotype was significantly lower than that of the control group (P<0.05). There was no significant difference in the frequencies of A1298C MTRR and A66G MTHFR between the two groups. The activity of MTHFR, red cell folate and plasma folate levels were significantly lower in URSA group than those of control group. Homocysteine levels were significantly higher in URSA group than those of control group (P<0.05). There were no significant differences in serum folic acid, red cell folate, homocysteine cysteine levels between patients <35 years old and ≥ 35 years old in URSA group. Conclusion C677TMTHFR gene polymorphism is associated with unexplained recurrent spontaneous abortion.

Effects of Folic Acid Supplement on Subjects with Different Methylenetetra-Hydrofolate Reductase C677T Genotypes / 天津医药

Objective To evaluate the effects of folic acid supplement on subjects with different 5, 10-methylenetet-rahydrofolate reductase (MTHFR) genotypes. Methods One hundred and eleven healthy women were divided into CC, CT and TT groups according to their MTHFR C677T genotypes. In each group subjects were randomly sub-divided into interven-tion (400 μg/d folic acid supplement) and control (usual diet) groups. The plasma folate, red blood cell (RBC) folate and plasma homocysteine (Hcy) concentration were measured at baseline and two months after intervention. Results The plasma folate was lower and the plasma Hcy was higher in the TT genotype than those in CC or CT genotypes (P＜0.05 or P＜0.01). After two months of intervention, the levels of plasma folate, RBC folate concentration increased while the plasma Hcy concen-tration decreased in all three intervention groups. Although the plasma folate concentration increased the most obvious in TT genotype than that of CC and CT genotypes, P＜0.05), the plasma Hcy concentration decreased the most obvious in TT geno-type than that of CT genotype, P＜0.05). Logistic regression analysis showed that the MTHFR TT genotype was a risk factor of high Hcy concentration, which was 8.078 times compared with that of CC genotype (P＜0.05). Conclusion Folic acid sup-plement can significantly increase plasma folate and red cell folate concentration, and reduce plasma Hcy concentration in all MTHFR genotypes. TT genotype was the most dangerous in disorder of folic metabolic and high Hcy concentration. However, low-dose folic acid supplement cannot reduce the risk of high Hcy concentration.