Expression of imprinted genes in placenta is associated with infant neurobehavioral development

Figures & data

Table 1. Descriptive characteristics of the study population (n = 615)

Characteristic	n	Frequency
Growth Status
Small for Gestational Age (SGA)	121	19.7%
Adequate for Gestational Age (AGA)	350	56.9%
Large for Gestational Age (LGA)	144	23.4%
Maternal Education
Less than high school	46	7.4%
High school	117	19.0%
Junior college/College +	452	73.5%
Maternal Marital Status
Married	385	62.6%
Single	230	37.4%
Household Income
< $25,000	135	22.0%
$25,000–$50,000	98	15.9%
$50,000-$75,000	104	16.9%
$75,000-$100,000	86	14.0%
$100,000+	128	20.8%
Not Sure/Refusal	64	10.4%
Infant Gender
Male	298	48.5%
Female	317	51.5%
NNNS Profile Membership
1	64	10.4%
2	107	17.4%
3	80	13.0%
4	98	15.9%
5	98	15.9%
6	106	17.2%
7	63	10.1%
Continuous Characteristic	Mean	SD
Gestational Age (Weeks)	39.04	0.95
Maternal Age	29.5	5.5

Table 2. NICU Network Neurobehavioral Scale (NNNS) score characteristics of the study population

NNNS Summary Score	Mean	SD	Min	Max	n
Arousal	4.17	0.77	2	6.33	615
Asymmetric reflexes	1.62	1.33	0	7	615
Attention	4.21	1.3	1.2	7.71	557
Excitability	4.47	2.83	0	13	615
Habituation	7.19	1.32	1	9	338
Handling	0.36	0.23	0	1	606
Hypertonicity	0.42	0.8	0	5	615
Hypotonicity	0.53	0.75	0	7	615
Lethargy	6.27	2.5	1	14	615
Non-optimal reflexes	5.91	2.11	0	11	615
Quality of Movement	4.16	0.66	1.8	5.67	614
Self-regulation	4.81	0.9	2.308	7.143	611
Stress/Abstinence	0.17	0.07	0	0.408	615

n indicates numbers of individuals within the population with that score available.

Figure 1. Heatmap of expression (total n = 615) for the 10 genes used to assign membership to clusters 1 (n = 319), 2 (n = 77), and 3 (n = 219).

Table 3. Top 10 genes by random Forest importance score for predicting an infant NNNS profile membership

Gene	Symbol	Random Forest Mean Decrease Accuracy Score
COPG2 Imprinted Transcript 1	COPG2IT1	8.04
24-dehydrocholesterol reductase	DHCR24	6.28
Distal-less homeobox 5	DLX5	9.33
Family with sequence similarity 50, member B	FAM50B	7.31
GNAS antisense RNA 1	GNAS-AS1	12.79
Nuclear pore associated protein 1	NPAP1	7.18
PAX8 antisense RNA 1	PAX8-AS1	8.72
Pleckstrin homology-like domain, family A, member 1	PHLDA1	7.2
SH3 and multiple ankyrin repeat domains 2	SHANK2	8.13
Vault RNA 2–1	VTRNA2–1	9.53

Figure 2. Of the 13 NNNS summary scores analyzed, 4 yielded differential scores based upon cluster assignments, including (A) infant stress, (B) quality of movement, (C) asymmetrical reflexes, and (D) non-optimal reflexes.

Table 4. Expression cluster membership and odds of an infant having an NNNS score within the sub-optimal 10th percentile of our population

Summary Score	Considered Risk	Cluster	Adjusted OR (95% CI)	P
Stress Abstinence	Score >90th percentile within our population (> 0.265).	1	Referent
		2	8.36 (3.28, 21.31)	< 0.001
		3	6.83 (3.07, 15.18)	< 0.001
Quality of Movement	Score <10th percentile within our population (<3 .33).	1	Referent
		2	1.16 (0.45, 3.04)	0.75
		3	2.10 (1.16, 3.83)	0.015
Asymmetrical reflexes	Score >90th percentile within our population (>3 .0).	1	Referent
		2	1.75 (0.98, 3.12)	0.058
		3	1.60 (1.06, 2.43)	0.026
Non-optimal reflexes	Score >90th percentile within our population (>9 .0).	1	Referent
		2	1.72 (0.81, 3.69)	0.16
		3	1.20 (0.66, 2.19)	0.55