Associations of green and blue space exposure in pregnancy with epigenetic gestational age acceleration

Figures & data

Figure 1. Spearman pairwise correlation between clinical and epigenetic gestational age. a) and b) estimated by Bohlin’s epigenetic clock in full group newborns (N = 1359) and in subgroup newborns with optimal pregnancy dating (N = 376), respectively. c) and d) estimated by Knight’s epigenetic clock in full group newborns and in subgroup newborns with optimal pregnancy dating, respectively.

Table 1. Maternal and newborn characteristics based on non-imputed data (n = 1359).

Maternal Characteristics
Age at intake (years)	31.7 (4.2)
Pre-pregnancy body mass index (kg/m^2)	24.2 (4.0)
Education
No or primary	25 (1.8%)
Secondary	442 (32.5%)
Higher	872 (64.2%)
Parity
Nulliparous	824 (60.6%)
Multiparous	533 (39.2%)
Smoking
Non-smoker or smoked until pregnancy was known	1069 (78.7%)
Smoked throughout pregnancy	179 (13.2%)
Neighbourhood deprivation index in tertiles
[1] low deprived	351 (25.8%)
[2] medium deprived	371 (27.3%)
[3] high deprived	633 (46.6%)
NDVI 100 m buffer	0.4 (0.3–0.5)
NDVI 300 m buffer	0.4 (0.3–0.5)
NDVI 500 m buffer	0.4 (0.4–0.5)
Major green space at 300 m (yes)	1137 (83.7%)
Distance to major green space (m)	146.5 (72.3, 248.5)
Major blue space at 300 m (yes)	762 (56.1%)
Distance to major blue space (m)	268.6 (127.1, 429.6)
Size of major blue space with (m^2)	23,918.9 (13,403.0, 64,974.4)
PM2.5	20.4 (18.1, 22.6)
Newborn Characteristics
Sex (girl)	668 (49.2%)
Birth weight (grams)	3548 (511)
Gestational age at birth (weeks)	40.2 (1.5)
Epigenetic gestational age (Bohlin, weeks)	39.3 (1.0)
Raw gestational age acceleration (Bohlin, weeks)	−0.9 (0.9)
Epigenetic gestational age (Knight, weeks)	36.3 (1.7)
Raw gestational age acceleration (Knight, weeks)	−3.8 (1.6)

Values are mean (SD) or median (1^st quartile, 3^rd quartile) for continuous variables and counts (%) for categorical variables. NDVI, normalized difference vegetation index. Missing values: maternal smoking, 111; maternal education, 20; maternal BMI, 8; neighbourhood deprivation index, 4; parity,2

Table 2. Associations of residential green and blue space in pregnancy and epigenetic gestational age acceleration based on Bohlin and Knight’s epigenetic clock in the full population (N = 1359) and sensitivity group (N = 376).

	Full population (N = 1359)				Subgroup with optimal pregnancy dating (N = 376)
	Raw Age Acceleration ^a		Residual Age Acceleration ^b		Raw Age Acceleration ^a		Residual Age Acceleration ^b
Bohlin’s Epigenetic Clock	Difference (95% CI)	p	Difference (95% CI)	p	Difference (95% CI)	p	Difference (95% CI)	p
NDVI 100 m	0.04 (−0.04, 0.11)	0.31	−0.02 (−0.06, 0.03)	0.42	−0.11 (−0.24, 0.03)	0.13	−0.03 (−0.12, 0.05)	0.42
NDVI 300 m	0.03 (−0.17, 0.05)	0.45	−0.03 (−0.08, 0.02)	0.24	−0.09 (−0.24, 0.06)	0.24	−0.04 (−0.13, 0.05)	0.42
NDVI 500 m	0.05 (−0.03, 0.13)	0.25	−0.03 (−0.08, 0.02)	0.31	−0.06 (−0.22, 0.09)	0.43	−0.04 (−0.13, 0.05)	0.37
Green space at 300 m	−0.11 (−0.03, 0.24)	0.11	0.05 (−0.03, 0.13)	0.25	0.13 (−0.12, 0.38)	0.31	0.04 (−0.11, 0.19)	0.61
Distance to green space	−0.17 (−0.54, 0.21)	0.38	−0.05 (−0. 27, 0.18)	0.68	−0.09 (−0.76, 0.57)	0.78	−0.13 (−0.53, 0.26)	0.51
Blue space at 300 m	−0.01 (−0.11, 0.09)	0.89	0.02 (−0.04, 0.08)	0.49	0.18 (−0.02, 0.37)	0.08	0.05 (−0.07, 0.17)	0.40
Distance to blue space	0.12 (−0.01, 0.34)	0.20	0.01 (−0.11, 0.14)	0.86	−0.19 (−0.60, 0.23)	0.37	−0.09 (−0.34, 0.16)	0.58
Blue space size	< −0.01 (< −0.01, <0.01)	0.86	< −0.01 (< −0.01, <0.01)	0.13	< −0.01 (−0.10, <0.01)	0.80	< 0.01 (−0.10, <0.01)	0.90
Knight’s Epigenetic Clock
NDVI 100 m	0.02 (−0.09, 0.13)	0.67	−0.02 (−0.12, 0.08)	0.70	−0.12 (−0.31, 0.06)	0.20	−0.07 (−0.23, 0.10)	0.41
NDVI 300 m	0.04 (−0.08, 0.16)	0.54	−0.01 (−0.22, 0.51)	0.90	−0.02 (−0.23, 0.19)	0.85	0.02 (−0.16, 0.20)	0.79
NDVI 500 m	0.04 (−0.09, 0.17)	0.56	−0.02 (−0.13, 0.09)	0.73	0.01 (−0.21, 0.22)	0.96	0.03 (−0.16, 0.21)	0.79
Green space at 300 m	0.04 (−0.16, 0.25)	0.69	−0.01 (−0.19, 0.17)	0.95	−0.04 (−0.38, 0.30)	0.83	−0.12 (−0.42, 0.18)	0.43
Distance to green space	−0.06 (−0.63, 0.51)	0.84	−0.02 (−0.48, 0.52)	0.93	0.21 (−0.70, 1.12)	0.64	0.12 (−0.60, 0.99)	0.63
Blue space at 300 m	−0.01 (−0.16, 0.14)	0.91	0.01 (−0.12, 0.15)	0.83	0.21 (−0.05, 0.48)	0.12	0.12 (−0.12, 0.35)	0.34
Distance to blue space	0.09 (−0.25, 0.42)	0.61	−0.01 (−0.31, 0.28)	0.94	−0.22 (−0.79, 0.35)	0.44	−0.16 (−0.65, 0.34)	0.54
Blue space size	< −0.01 (< −0.01, <0.01)	0.43	< −0.01 (< −0.01, <0.01)	0.81	< −0.01 (−0.10, <0.01)	0.55	< −0.01 (−0.10, <0.01)	0.37

Values represent regression coefficients (95% confidence interval) and reflect the difference in raw and residual gestational age acceleration at birth per increase of 1 interquartile range for NDVI, 1 kilometre for green and blue space distances, and 1 square kilometre for blue space size. Results are based on the main models, which were adjusted for maternal age, education, parity and smoking, child sex, batch effects (by including plate number), and estimated cell proportions.

NDVI, normalized difference vegetation index; CI, confidence interval

^aRaw gestational age acceleration (in weeks) was obtained by subtracting the clinical estimate of gestational age from DNA methylation gestational age

^bResidual gestational age acceleration (in weeks) was calculated from the residuals from a regression model of DNA methylation gestational age on clinical gestational age

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