Maternal dyslipidemia during early pregnancy and epigenetic ageing of the placenta

Figures & data

Table 1. Characteristics of study participants.

Characteristics	n = 262
Gestational age (weeks) at first visit, mean (s.d.)	12.72 (0.93)
Gestational age (weeks) at delivery, mean (s.d.)	39.46 (1.13)
Placental DNA methylation age, weeks, mean (s.d.)	38.07 (1.53)
Placental Age Acceleration, weeks, mean (s.d.)	−1.39 (1.79)
Offspring female sex n (%)	131 (50.0)
Maternal age, years	27.54 (5.24)
Pre-pregnancy BMI, kg/m^2, mean (s.d.)	23.3 (2.90)
Normal BMI (<25), n(%)	185 (70.88)
Overweight or obese (≥25), n (%)	76 (29.12)
Race/ethnic group, n (%)
White	65 (24.81)
Black	61 (23.28)
Hispanic	88 (33.59)
Asian	48 (18.32)
High school or less education, n (%)	798(29.77)
Married or living with partner, n (%)	195 (74.71)
Employed/Student, n (%)	182 (69.47)
Private health insurance, n (%)	161 (61.45)
Preeclampsia-Yes, n (%)	7 (2.67)
High-density lipoprotein cholesterol (HDLc), n (%)
Low HDLc (<50 mg/dl)	38 (14.50)
Low-density lipoprotein cholesterol (LDLc), n (%)
High LDLc (≥100 mg/dl)	122 (46.56)
Triglycerides, n (%)
High triglycerides (≥150 mg/dl)	52 (19.85)
Total cholesterol (TChol), n (%)
High TChol (≥200 mg/dl)	77 (29.39)

Table 2. Association between maternal dyslipidemia and placental epigenetic age acceleration.

			Prepregnancy BMI^b				Offspring sex^c
	Overall^a		Normal weight		Overweight or Obese		Male		Female
Lipids	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P
Normal HDLc Low HDLc	Reference 0.41 (-0.27, 1.08)	0.23	Reference 0.82 (0.00, 1.64)	0.04	Reference -0.32 (-1.62, 0.98)	0.63	Reference -0.31 (-1.22, 0.59)	0.50	Reference 1.20 (0.17, 2.24)	0.02
Normal LDLc High LDLc	Reference 0.05 (-0.41, 0.51)	0.84	Reference 0.03 (-0.53, 0.59)	0.91	Reference 0.40 (-0.52, 1.31)	0.39	Reference -0.21 (-0.84, 0.43)	0.52	Reference 0.22 (-0.47, 0.90)	0.53
Normal triglycerides High triglycerides	Reference -0.37 (-1.02, 0.28)	0.27	Reference -0.48 (-1.27, 0.31)	0.24	Reference -0.16 (-1.44, 1.12)	0.81	Reference 0.16 (-0.69, 1.02)	0.71	Reference -0.83 (-1.83, 0.16)	0.10
Normal TChol High TChol^d	Reference 0.07 (-0.42, 0.57)	0.78	Reference -0.09 (-0.73, 0.55)	0.79	Reference 0.85 (-0.07, 1.76)	0.07	Reference 0.03 (-0.67, 0.73)	0.93	Reference -0.001 (-0.74, 0.73)	1.00

^aModel included HDLc, LDLc, triglycerides, race/ethnic group, pre-pregnancy obesity status, offspring sex, education, marital status, health insurance, employment, age, gestational age during blood sample collection, preeclampsia status;

^bModel included HDLc, LDLc, triglycerides, race/ethnic group, offspring sex, education, marital status, health insurance, employment, age, gestational age during blood sample collection, preeclampsia status;

^cModel included HDLc, LDLc, triglycerides, race/ethnic group, pre-pregnancy obesity status, education, marital status, health insurance, employment, age, gestational age during blood sample collection, preeclampsia status;

^dModels for TChol included all covariates except HDLc, LDLc, and triglycerides;

HDLc, High-density lipoprotein cholesterol; LDLc, Low-density lipoprotein cholesterol; TChol, Total cholesterol.

Figure 1. Odds of positive placental age acceleration among women with low HDLc compared to women with normal HDLc. Comparisons were made among all participants (overall), among women with pre-pregnancy normal weight and overweight/obese (BMI), and among gestations with male and female fetuses (sex).

Table 3. Association between maternal dyslipidemia and placental epigenetic age acceleration in four race/ethnic groups.

			Whites, n = 67		Blacks, n = 63		Hispanics, n = 89		Asians, n = 48
Lipids			β (95% CI)	P	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P
High-density lipoprotein cholesterol
Normal			Reference		Reference		Reference		Reference
Low	Overall^a		−0.18 (-1.88, 1.52)	0.84	0.28 (-1.49, 2.04)	0.75	0.70 (-0.38, 1.79)	0.20	2.80 (0.76, 4.84)	0.01
	Normal weight^b		0.25 (-1.89, 2.38)	0.81	0.03 (-3.59, 3.64)	0.99	1.50 (0.13, 2.88)	0.03	2.56 (0.20, 4.91)	0.03
	Overweight or Obese ^b		-1.73 (-6.76, 3.29)	0.43	0.66 (-2.20, 3.53)	0.62	-1.02 (-3.46, 1.43)	0.39	NA	0.03
	Male^c		−1.25 (-4.84, 2.34)	0.47	−0.32 (-2.72, 2.07)	0.78	−0.06 (-1.31, 1.19)	0.93	−1.23 (-5.95, 3.49)	0.59
	Female^c		0.96 (-1.51, 3.43)	0.43	3.03 (0.11, 5.96)	0.04	1.54 (-0.40, 3.47)	0.12	4.90 (-0.31, 10.11)	0.06
Low-density lipoprotein cholesterol
Normal			Reference		Reference		Reference		Reference
High	Overall^a		0.90 (-0.14, 1.93)	0.09	−0.19 (-1.24, 0.85)	0.71	−0.26 (-1.18, 0.65)	0.57	0.13 (-0.95, 1.20)	0.81
	Normal weight^b		0.44 (-0.82, 1.70)	0.48	−0.49 (-2.35, 1.37)	0.59`	−0.18 (-1.35, 0.99)	0.76	0.21 (-1.01, 1.42)	0.73
	Overweight or Obese ^b		1.41 (-1.28, 4.09)	0.25	0.24 (-1.87, 2.36)	0.81	-0.41 (-2.54, 1.71)	0.68	NA	0.73
	Male^c		−0.58 (-2.52, 1.37)	0.54	−1.08 (-2.86, 0.70)	0.22	−0.52 (-1.71, 0.67)	0.38	−0.84 (-2.65, 0.97)	0.34
	Female^c		0.58 (-1.02, 2.19)	0.46	-0.67 (-2.11, 0.77)	0.34	-0.09 (-1.56, 1.38)	0.90	0.19 (-2.23, 2.62)	0.86
Triglycerides
Normal			Reference		Reference		Reference		Reference
High	Overall^a		−0.97 (-2.57, 0.63)	0.23	−0.88 (-3.14, 1.39)	0.44	−0.22 (-1.48, 1.04)	0.73	0.09 (-1.14, 1.33)	0.88
	Normal weight^b		−1.34 (-4.06, 1.37)	0.32 0.33	−0.97 (-4.58, 2.65)	0.59	−0.49 (-1.98, 0.99))	0.51	0.12 (-1.24, 1.48)	0.86
	Overweight or Obese ^b		-1.37 (-4.53, 1.80)	0.33	-0.01 (-4.28, 4.26)	1.00	-0.05 (-2.85, 2.76)	0.97	NA	0.86
	Male^c		−3.23 (-6.67, 0.21)	0.06	0.62 (-2.10, 3.34)	0.64	0.60 (-0.90, 2.10)	0.42	1.17 (-0.72, 3.07)	0.21
	Male^c		−3.23 (-6.67, 0.21)	0.06	0.62 (-2.10, 3.34)	0.64	0.60 (-0.90, 2.10)	0.42	1.17 (-0.72, 3.07)	0.21
Total Cholesterol^d
Normal			Reference		Reference		Reference		Reference
High	Overall^a		1.28 (0.12, 2.45)	0.03	−0.15 (-1.18, 0.88)	0.77	−0.10 (-1.10, 0.89)	0.83	−0.16 (-1.36, 1.03)	0.78
	Normal weight^b		0.87 (-0.63, 2.38)	0.25	−0.52 (-2.36, 1.33)	0.57 0.44	−0.61 (-1.85, 0.63)	0.33	−0.07 (-1.39, 1.25)	0.92
	Overweight or Obese ^b		-0.32 (-2.11, 1.47)	0.71	0.64 (-1.08, 2.36)	0.44	1.79 (-0.08, 3.66)	0.06	NA	0.92
	Male^c		1.43 (-0.89, 3.75)	0.21	−1.05 (-2.49, 0.39)	0.14	0.64 (-0.68, 1.97)	0.33	0.005 (-1.64, 1.65)	1.00
	Female^c		0.98 (-0.46, 2.43)	0.17	-0.32 (-2.11, 1.47)	0.71	-0.55 (-2.02, 0.91)	0.45	-0.84 (-3.55, 1.88)	0.51

^aModel included HDLc, LDLc, triglycerides, race/ethnic group, pre-pregnancy obesity status, offspring sex, education, marital status, health insurance, employment, age, gestational age during blood sample collection, preeclampsia status;

^bModel included HDLc, LDLc, triglycerides, race/ethnic group, offspring sex, education, marital status, health insurance, employment, age, gestational age during blood sample collection, preeclampsia status;

^cModel included HDLc, LDLc, triglycerides, race/ethnic group, pre-pregnancy obesity status, education, marital status, health insurance, employment, age, gestational age during blood sample collection, preeclampsia status;

^dModels for TChol included all covariates except HDLc, LDLc, and triglycerides;

Whites: 48 normal weight and 19 overweight or obese; Blacks: 38 normal weight and 24 overweight or obese; Hispanics: 61 normal weight and 28 overweight or obese; Asians: 42 normal weight and 6 overweight or obese; NA, model was not run because there was only one Asian who was overweight or obese.