Fetal growth in environmental epidemiology: mechanisms, limitations, and a review of associations with biomarkers of non-persistent chemical exposures during pregnancy

Kamai, Elizabeth M.; McElrath, Thomas F.; Ferguson, Kelly K.

doi:10.1186/s12940-019-0480-8

Environmental Health

Table 2 Studies of maternal prenatal urinary phthalate metabolites and fetal growth outcomes measured in utero

From: Fetal growth in environmental epidemiology: mechanisms, limitations, and a review of associations with biomarkers of non-persistent chemical exposures during pregnancy

Reference	Country, years	N	Urinary phthalate metabolites	Timing of urine collection	in utero outcome(s)	Timing of outcome assessment	Notes¹	All²	Girls²	Boys²
Zhao et al. 2014 [97]	China 2012-2013	126	MBP, MMP ∑DEHP: MEHP, MEHHP, MEOHP	3^rd trimester	IUGR	3^rd trimester		+ IUGR (MEHHP)
Zhao et al. 2015 [126]	China 2011-2013	119	MBP, MMP ∑DEHP: MEHP, MEHHP, MEOHP	3^rd trimester	Growth restricted (IUGR or low birth weight)	not specified		+ Growth restricted (MEHP, MEHHP, MEOHP, ∑DEHP)
							<37 weeks only	NS
							≥37 weeks only	+ Growth restricted (MEHHP, MEOHP, ∑DEHP)
Botton et al. 2016 [99]	France 2003-2006	520	∑LMW: MEP, MBP, MiBP ∑HMW: MBzP, MCOP, MCPP, MCNP, MECPP, MEHHP, MEOHP, MEHP ∑DEHP: MECPP, MEHHP, MEOHP, MEHP	26 weeks	EFW AC BPD HC FL	12 weeks				̵ BPD (MBzP, ∑HMW, MECPP, MEHHP, MEOHP, ∑DEHP)
						22 weeks				- EFW (MBzP, MCNP) - BPD (MBzP, MCPP, ∑HMW, MECPP, MEHHP, MEOHP, MEHP, ∑DEHP) + FL (MCNP)
						32 weeks				- BPD (MCPP, ∑HMW, MECPP, MEHHP, MEOHP, MEHP, ∑DEHP) + FL (MCNP)
						overall pregnancy				- EFW (∑HMW, MECPP, MEHHP) - BPD (MBzP, ∑HMW, MECPP, MEOHP, ∑DEHP) + FL (MCNP)
Casas et al. 2016 [100]	Spain 2004-2006	390	MBzP ∑LMW: MEP, MiBP, MnBP; ∑DEHP: MEHP, MEHHP, MEOHP, MECPP	12, 32 weeks**	EFW AC BPD HC FL	12 weeks	not adjusted for GA	NS	NS	NS
						20 weeks		- HC (MnBP)	NS	NS
						34 weeks		+ FL (MBzP)	+ FL (MBzP)	NS
						growth rate 12-20 weeks		- EFW (MnBP) - HC (MnBP)	- HC (MnBP)	- HC (MnBP)
						growth rate 20-34 weeks		+ FL (MBzP)	+ FL (MBzP)	+ EFW (MnBP) + AC (MnBP)
Ferguson et al. 2016 [101, 102]	USA 2006-2008	482	MEP, MBP, MiBP, MBzP, MCPP ∑DEHP: MECPP, MEHHP, MEOHP, MEHP	10, 18, 26, 35 weeks**	EFW AC HC FL	26, 35, 38 weeks		- EFW (MEOHP, MECPP, ∑DEHP) - AC (MECPP, ∑DEHP) - HC (MECPP, MBzP) - FL (MECPP, ∑DEHP)	- EFW (MECPP, ∑DEHP) - HC (MEP)	- AC (∑DEHP) - FL (MEHHP, MEOHP, ∑DEHP)

¹Unless otherwise specified, studies included term, preterm, parous, and nulliparous births, and models of birth outcomes adjusted for or standardized to gestational age.
²Blank cells indicate associations were not examined; NS indicates that associations within that category were examined but not statistically significant at p<0.05.
*Average of two or more urine samples.
Abbreviations. AC, abdominal circumference; BPD, biparietal diameter; EFW, estimated fetal weight; FL, femur length; GA, gestational age; HC, head circumference; IUGR, intrauterine growth restriction, defined as estimated fetal weight below the 10^th centile for gestational age; MBP, monobutyl phthalate; MBzP, monobenzyl phthalate; MCOP, monocarboxy-isooctyl phthalate; MCNP, monocarboxy-isononyl phthalate; MCPP, mono-3-carboxypropyl phthalate; MEP, monoethyl phthalate; MECPP, mono-2-ethyl-5-carboxypentyl phthalate; MEHHP, mono-2-ethyl-5-hydroxyhexyl phthalate; MEHP, mono-2-ethylhexyl phthalate; MEOHP, mono-2-ethyl-5-oxohexylphthalate; MiBP, monoisobutyl phthalate; MMP, monomethyl phthalate; MnBP, mono-n-butyl phthalate; ∑DEHP, molar sum of the di-2-ethylhexyl phthalate metabolites that follow; ∑HMW, molar sum of the high molecular weight phthalate metabolites that follow; ∑LMW, molar sum of the low molecular weight phthalate metabolites that follow.

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