孕期環境因子暴露對子代健康之影響

Environmental exposure and health effect in a mother-infant study

黃世惠(Shih-Hui Huang)

指導教授 ： 吳明蒼

高雄醫學大學/健康科學院/公共衛生學系環境暨職業安全衛生博士班/博士(2017年)

摘要

我們已知在胚胎早期若受到毒性物質的危害是最容易影響其胎兒生長,而且影響久遠。在孕期暴露於菸害對胎兒有很多危害，例如:低體重、早產等;微量元素(如:鐵、銅、錳)對於人體是必須的礦物質，但過量卻是有毒的。孕婦暴露於必需微量元素(錳、銅、鐵)和重金屬(汞)、菸害對胎兒的健康效應，是一個全世界婦女都關心的重要議題。而在醫學方面，台灣很少有同時具有成對的孕婦/胎兒全血中的必需微量元素和重金屬濃度的相關資料可利用。因此本研究分為二部分來探討孕期環境因子暴露對子代健康之影響。第一部分 探討孕期暴露於菸害(Cotinine)對出生結果的影響;第二部分探討孕期暴露於重金屬的母嬰研究(1)評估成對孕婦和胎兒之間全血中汞(Hg)、錳(Mn)、鐵(Fe)和銅(Cu)濃度的相關性; (2)研究懷孕期間潛在的干擾因子;(3)分析母親海鮮攝取量及維他命對母血及臍帶血中汞濃度的影響。
本研究的對象：2009年2月至2011年5月，到屏東縣輔英科技大學東港附設醫院婦產科進行產檢之懷孕孕婦並同意參與本研究。及該孕婦於輔英科技大學附設醫院婦產科生產之新生兒。在孕婦第三孕期28-30週產檢時抽血及收集尿液、問卷。新生兒資料由病歷中抄錄。
第一部分研究結果發現:研究對象中有7.2%抽菸, 而有40.6% 的孕婦孕期暴露在二手菸或環境菸害. 孕婦分為三組:(1)不抽菸(2)二手菸(3)抽菸，不抽菸這組孕婦其所生的子代體重較重，且三組比較呈顯著差異, 胸圍較大，出生後3天膽紅素較
高 , 尿中cotinine 濃度較低。當母親暴露於菸害增加時，驗出尿中cotinine ?d 143 μg/g creatinine;且發現其出生新生兒體重<2500公克的危險性是3.39倍。當母親尿驗出cotinine <143 μg/g creatinine比cotinine ?d 143 μg/g creatinine，新生兒出生體重較重，胸圍較大，出生後第3天膽紅素較高。
第二部分研究結果發現在孕婦/胎兒的成對樣本中重金屬濃度皆呈正相關; 汞(r = 0.78，p < 0.001)，錳(r = 0.31，p < 0.001)，鐵(r=0.17，p = 0.038)和銅(r= 0.21，p= 0.010)。42.1%(61人)母親懷孕時一星期吃大於3次以上的維他命(>3 次/星期)與母血中較低汞濃度有顯著差異(調整過的 odds ratio 0.272, p= 0.005);與母血中較低銅濃度亦有顯著差異(調整過的odds ratio 0.267, p = 0.004)。胎兒臍帶血對應其母血，其血中汞、錳、鐵濃度的中位數高於母血中濃度；而臍帶血中銅的濃度則低於母血濃度。61.9%(78人)在懷孕時吃大量的海產，這些人有2.91倍的危險性(調整後勝算比2.91,95%信賴區間:1.04-8.15,p=0.042)會血中汞濃度高於5.8µg/L.而母親在懷孕前一星期吃超過3次維他命者，被發現血中汞濃度低於5.8µg/L(調整後勝算比 0.06, 95% CI: 0.01-049, p= 0.008)。
在此系列研究中顯示孕婦抽菸與新生兒低體重、胸圍小有關，台灣的孕婦抽菸盛行率低但大部分暴露在二手菸的環境下，將來的研究應評估有用的介入讓孕婦處於無菸環境; 這項研究也表明成對孕婦與胎兒臍帶血之間：汞、鐵、銅、錳呈正相關。大量海鮮的攝食是母血高濃度汞的危險因子。我們的發現也提高了懷孕時可藉由吃維他命來降低母體中汞和銅的血中濃度的可能性。將來的研究應該著重在調查維他
命對汞濃度的影響。
最終目的是藉由流行病學研究逐步建立台灣南部地區孕婦及胎兒重金屬之參考濃度，以提供孕婦、嬰兒有關重金屬後續研究的參考。

關鍵字

孕婦 ； cotinine ； 二手菸 ； 出生結果 ； 膽紅素 ； 海鮮 ； 重金屬 ； 維他命

並列摘要

It is well documented that smoking exposure during pregnancy is associated with multiple adverse effects on the fetus. Active maternal smoking increases the risks of preterm delivery, miscarriage, low birth weight (LBW), etc. The effect of maternal exposure to essential minerals and heavy metals on the fetus is an important issue, which affects women around the world. Few data are available on the concentration of both essential minerals and heavy metals in maternal/fetal medicine.
So, this study" Prenatal environmental exposure and health effect in a mother-infant study" had two parts. Part Ⅰ: Prenatal exposure cotinine in the mother-infant study. To evaluate the effect of maternal smoking exposure during pregnancy on postnatal outcomes. Part Ⅱ: Prenatal exposure heavy metal (Hg, Mn, Fe, Cu) in mother-infant study. The aims of this study were to (1) assess the correlation of mercury (Hg), manganese (Mn), iron (Fe), and copper (Cu) in paired maternal/fetal blood samples, and (2) study potential confounding factors during pregnancy.(3)examine the influence of maternal seafood consumption and vitamin supplementation during pregnancy on maternal and umbilical cord blood mercury (Hg) concentration.
This is a cross-section study. Healthy pregnant women enrolled pregnant women were recruited at the Department of Obstetrics and Gynecology of Fooyin University Hospital in Tong Gang, Taiwan, from February 2009 to May 2011 The research protocol was approved by the Institutional Review Board of Fooyin University, and written informed consent was obtained from all participants. Information on the gestational age, prenatal examination, and characteristics of the birth and newborn obtained from the medical records. We used interviewer-administered questionnaires to collect information on demographic characteristics, smoking habits, alcohol drinking habits, betel nut chewing habits, use of Chinese medicine, seafood consumption, nutritional supplement (vitamin), and degree of education.
PartⅠresults:
A minority of subjects (7.2%) smoked, while 40.6% of subjects were exposed to environmental tobacco smoke during pregnancy. There was significantly higher birth weight (3205.2 ± 373.1 vs 3089.7 ± 363.0 vs 2959.0 ± 403.7 g, p = 0.004), larger chest size (33.1 ± 1.7 cm vs 32.7 ± 1.5 cm vs 32.0 ± 1.7 cm, p = 0.009), higher bilirubin on postnatal day 3 (8.9 ± 1.6 vs 8.6 ± 1.5 vs 7.8 ± 1.4 mg/dL, p = 0.015), but lower maternal urinary cotinine level (83.7 ± 132.4 vs 153.2 ± 96.0 vs 800.5 ± 1027.8 μg/g creatinine, p < 0.001) in smoking-free status than in passive or active smoking status. Significant risks of birth weight < 2500 g (AOR 3.93 (95% CI 1.61-9.59), p = 0.003) and maternal urinary cotinine ³ 143 μg/g creatinine (AOR 3.38 (95% CI 2.02-5.66), p < 0.001) were observed as smoking exposure increased. There was significantly higher birth weight (p = 0.048), larger chest size (p = 0.045), and higher bilirubin level on postnatal day 3 ( p < 0.001) in the group with cotinine <143 μg/g creatinine than in the group with cotinine ³ 143 μg/g creatinine.
Part Ⅱresults:
There was a positive correlation of Hg (r = 0.78, p < 0.001), Mn (r = 0.31, p < 0.001), Fe (r=0.17, p = 0.038), and Cu (r= 0.21, p= 0.010) in paired maternal/fetal samples. Prenatal vitamin use (>3 times/wk) was significantly associated with lower maternal Hg (adjusted odds ratio 0.272, p= 0.005) and lower maternal Cu (adjusted odds ratio 0.267, p = 0.004) levels. Median fetal Hg, Mn, and Fe levels were higher than corresponding maternal levels, while median fetal Cu level was lower than maternal Cu level. Sixty-one of these women (42.1%) used vitamins > 3 times/week prenatally. Seventy-eight of our subjects (61.9 %) reported eating higher amounts of seafood during the pregnancy. Mothers with high seafood consumption had a 2.91-fold greater risk (adjusted odds ratio 2.91, 95% CI: 1.04-8.15, p=0.042) of high Hg levels (>5.8µg/L). However, mothers whose prenatal vitamin intake > 3 times/week were found to have low Hg levels (<5.8µg/L) (adjusted odds ratio 0.06, 95% CI: 0.01-049, p= 0.008).
Conclusion:
In this series, we found that maternal smoking exposure during pregnancy is associated with low birth weight and small chest circumference. The incidence of active smoking in Taiwanese pregnant women is low, but most of them are exposed to the passive smoking environment. Further studies are required to evaluate useful interventions in enhancing smoking-free environment during pregnancy.
There is a positive correlation of Hg, Fe, Cu, and Mn in paired maternal/fetal samples in this series. Our findings have raised the possibility of reducing maternal Hg and Cu by way of prenatal vitamin supplementation.
These data may contribute to establishing reference levels in pregnant women, and study the role and mode of action of environmental metals in both mother and the fetus.

並列關鍵字

pregnancy ； birth outcome ； cotinine ； bilirubin ； copper ； iron ； manganese ； mercury ； vitamin ； seafood

參考文獻

part 1 參考文獻

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