Second trimester extracellular microRNAs in maternal blood and fetal growth: An exploratory study

Figures & data

Table 1. Summary of study participants' characteristics.

		Matched groups
Characteristic^a	All Participants^b	SGA^b	AGA^b	LGA^b
n	100	36	51	13	P value^d
Maternal
Age (years)	27.8 ± 6.1	26.0 ± 6.1	28.4 ± 5.8	30.6 ± 6.4	0.03
Height (cm)	154.4 ± 5.1	153.4 ± 5.4	154.7 ± 4.8	156.0 ± 4.9	0.09
Body weight (kg)	62.7 ± 9.5	61.0 ± 10.8	61.8 ± 7.9	71.2 ± 7.6	0.001
Body mass index (BMI) (kg/m^2)	26.3 ± 3.7	25.9 ± 4.1	25.8 ± 3.3	29.2 ± 2.6	0.003
Hemoglobin levels (g/dL)	12.8 ± 1.0	13.0 ± 1.1	12.7 ± 0.9	12.7 ± 1.4	0.44
Multiparous; n (%)	65 (65.0)	20 (55.6)	34 (66.7)	11 (84.6)	0.17
Alcohol consumption; n (%)					0.72
Yes	6 (6.0)	3 (8.3)	3 (5.9)	0 (0.0)
No	94 (94.0)	33 (91.7)	48 (94.1)	13 (100.0)
Socioeconomic status; n (%)					0.93
Low	49 (49.0)	17 (47.2)	25 (49.0)	7 (53.8)
Medium	40 (40.0)	15 (41.7)	21 (41.2)	4 (30.8)
High	11 (11.0)	4 (11.1)	5 (9.8)	2 (15.4)
Smoke exposure in the home^e; n (%)					0.49
Yes	28 (28.6)	9 (25.7)	17 (33.3)	2 (16.7)
No	70 (71.4)	26 (74.3)	34 (66.7)	10 (83.3)
Infant
Birth weight (g)	3014 ± 633	2396 ± 220	3190 ± 393	4038 ± 331	<0.0001
Gestational age (weeks)^f	38.3 ± 1.0	38.2 ± 1.0	38.3 ± 1.1	38.3 ± 1.0	0.89
Birthweight-for-gestational age^g (z-score)	−0.6 ± 1.3	−1.9 ± 0.4	−0.2 ± 0.7	1.5 ± 0.3	<0.0001
Sex^f; n (%)					1.00
Males	51 (51.0)	18 (50.0)	26 (51.0)	7 (53.8)
Females	49 (49.0)	18 (50.0)	25 (49.0)	6 (46.2)

^a All maternal information was collected during the second trimester visit (16-22 weeks).

^b All values are shown as mean ± SD, unless otherwise noted.

^c Participants in the SGA, AGA, and LGA groups were matched by gestational age at delivery and infant's sex.

^d P value corresponds to Chi squared (continuous) or Fisher's exact (categorical) test for the difference in study participants' characteristics between SGA, AGA, and LGA groups.

^e Data are missing for 2 participants.

^f Variables used to match controls (LGA) to cases (SGA or LGA).

^g Adjusted for gestational age and infant sex.

Figure 1. Odds ratios for having an SGA or LGA vs. AGA infant in association with levels of extracellular microRNAs (exmiRNAs) in maternal serum. Odds ratios are adjusted for gestational age and infant's sex; -log₁₀ (P Value) indicates transformed P values of the association between exmiRNAs and SGA or LGA. Odds ratios between SGA and AGA are shown in white and between LGA and AGA in gray.

Figure 2. Associations between extracellular microRNAs (exmiRNAs) in maternal serum and birth weight-for-gestational age z-score (n = 100). Volcano plot showing the association between serum exmiRNAs at second trimester and birth weight-for-gestational age z-score; estimates are adjusted for maternal age, gestational age, body mass index, parity, and infant's sex; -log₁₀ (P value) indicates transformed P values of the association between exmiRNAs and birth weight-for-gestational age z-score.

Figure 3. Pathway analysis illustrating experimentally validated mRNA targets of the most associated exmiRNAs with fetal growth. Biological relevance with functions and diseases related to fetal growth is also identified by the Ingenuity Pathway Analysis®. Direct relationships are represented with solid lines and indirect relationships with dotted lines.

Figure 4. Fold change of serum extracellular microRNAs (exmiRNAs) between mothers of small- and appropriate-for-gestational age infants by gender. Volcano plot showing the fold change of all tested serum exmiRNAs at second trimester from mothers of male (white) and female (gray) SGA vs. AGA infants. *Denotes exmiRNAs in female mother-infant pairs.

Figure 5. Fold change of serum extracellular microRNAs (exmiRNAs) between mothers of large- and appropriate-for-gestational age infants by gender. Volcano plot showing the fold change of all tested serum exmiRNAs at second trimester from mothers of male (white) and female (gray) LGA vs. AGA infants.