Association Of Maternal Thyroid Function During Pregnancy With Placental Morphology,Inflammatory And Oxidative Stress Response: A Cohort Study

ObjectiveTo elucidate the association between maternal FT₄,TSH and TPOAb levels and trajectories during pregnancy with placental morphology and expression of inflammatory and oxidative stress cytokines.MethodsBased on the Ma’anshan Birth Cohort（MABC）,3474 pregnant women who underwent their first obstetric examination at Ma’anshan Maternal and Child Health Hospital from May 2013 to September 2014 were included in the study.Basic demographic information on pregnant women and delivery-related information was collected through questionnaire survey as well as clinical information extracts.Using the opportunity of obstetric examination,fasting venous blood was collected from pregnant women in early,middle and late pregnancy,and the levels of thyroid hormones（FT₄,TSH）and thyroid autoantibody TPOAb in the mother’s serum were retrospectively dosed by electrochemical immunoassay.The gross morphology of the placenta（placenta length,width,thickness）was measured and placental tissue was collected at the time of delivery.Placental surface area,volume,weight,efficiency and eccentricity were calculated according to the equations.The expression of m RNA levels of 10 placental inflammatory and oxidative stress cytokines was measured by real-time fluorescence quantitative PCR.The basic demographic characteristics of the included and excluded study subjects were compared by usingχ²test and independent samples t-test.Generalized linear models were used to analyze the association between maternal thyroid function and placental morphology and inflammatory and oxidative stress cytokines at different gestations.The False Discovery Rate（FDR）correction was used to adjust for multiple significance tests,and adjusted P values were calculated according to the Benjamini-Hochberg（BH）method.A growth mixture model was used to fit trajectories to the raw data of maternal FT₄,TSH and TPOAb in early,mid and late pregnancy.A generalized linear model was used to analyze the association between trajectories and placental indicators.ResultsOf the 2639 mother-child pairs included in this study,mothers included were at an average age of（26.6±3.6）years.Mothers had（13.4±3.1）years of education and gained（17.9±5.0）kg during pregnancy.A total of 2356（89.3%）of the mothers were primiparous.Most of the mothers had no experience of smoking and alcohol consumption before or during pregnancy（95.9%and 92.0%,respectively）.Only 321（12.2%）,145（5.5%）and 213（8.1%）mothers had adverse pregnancy complications.The infants were born at（39.1±1.2）weeks gestational age and had a birth weight of（3279.5±532.6）g.There were 1345（51.0%）male and 1291（49.0%）female infants.After adjusting for relevant confounding factors,TPOAb levels were negatively correlated with placental eccentricity in early gestation.In mid-gestation,FT₄levels were negatively correlated with placental length,width,area,volume,and weight;TPOAb levels were negatively correlated with placental length and area.In late gestation,FT₄levels were negatively correlated with placental length and width;TPOAb levels were negatively correlated with placental length and width as well as area.Compared to moderate-level FT₄trajectory,low-level FT₄trajectory tended to increase placental length width,area,volume,and weight and decrease placental efficiency.Compared to low-level TSH trajectories,moderate-level TSH trajectories tended to increase placental length and area.The high-level trajectory tended to decrease placental length and area compared to the low-level TPOAb trajectory.FT₄levels in early pregnancy were positively correlated with placental pro-inflammatory cytokines（IL-1β,IL6,TNF-α）and oxidative stress cytokines（HO-1,HIF-1α,GRP78）.TPOAb levels in early pregnancy were positively correlated with placental pro-inflammatory cytokines（IL6,TNF-α,CRP）,anti-inflammatory cytokine IL-10,and oxidative stress cytokines（HO-1,HIF-1α,GRP78）.FT4 levels in late pregnancy were positively correlated with the expression of pro-inflammatory cytokines IL-1βand TNF-α.The low-level FT₄trajectory tended to reduce pro-inflammatory and oxidative stress cytokines,while the medium-level TSH trajectory was the opposite.ConclusionMaternal thyroid function affects placental morphology and inflammatory and oxidative stress responses in a pregnancy-dependent manner.Maternal FT₄and TPOAb levels have a significantly effect on placental length and area,mid-and late gestation may be the sensitive period.FT₄and TPOAb levels significantly affect placental pro-inflammatory and oxidative stress levels,early gestation may be a sensitive period.Changes in dynamic trajectory of thyroid function indicators during pregnancy affect placental morphology and functional indicators.