Excessive gestational weight gain and obesity contribute to altered expression of maternal insulin-like growth factor binding protein-3

Figures & data

Table 1 Patient characteristics

Patient characteristics	GWG ADHERE	GWG EXCEED
Age (y)	33.88 (6.6)	32.31 (5.0)
Height (m)	1.62 (0.9)	1.63 (0.7)
Pregravid weight (kg)	64.07 (20.0)	86.92 (22.3)*
BMI (kg/m^2)	24.51 (8.7)	32.75 (9.8)*
Parity	2.38 (0.7)	2.08 (0.4)
Gestational age (wk)	38.38 (1.1)	38.77 (0.9)
Prenatal GCT (mmol/L)	6.36 (1.9)	6.39 (1.3)
HOMA-IR (log)	0.22 (0.1)	0.52 (0.3)
Absolute GWG (kg)	11.89 (3.6)	14.97 (4.5)
% exceed IOM upper limit	78.21 (18.0)	136.82 (33.6)*
Infant birth weight (g)	3,216.25 (505.8)	3,547.77 (310.1)
Placenta weight (g)	731.00 (157.9)	742.83 (94.7)
Fetal–placental weight ratio	4.47 (0.5)	4.87 (0.6)

Notes: Data presented mean (standard deviation).

* Denotes P ≤ 0.05.

Abbreviations: BMI, body mass index; GCT, glucose challenge test; GWG, gestational weight gain; HOMA-IR, homeostasis model of assessment for insulin resistance; % exceed IOM, Institute of Medicine upper limit of GWG based on prepregnancy BMI.

Figure 1 Excessive gestational weight gain augments maternal IGFBP-3 expression. Representative serum expression patterns of glycosylated (g) and nonglycosylated (ng) maternal IGFBP-3 isoforms of patients who adhere to (ADHERE) or exceed (EXCEED) the 2009 IOM GWG guidelines.

Note: *Denotes P ≤ 0.05.
Abbreviations: IC, internal control; GWG, gestational weight gain; IGFBP-3, insulin-like growth factor binding protein-3; IOM, Institute of Medicine.

Figure 2 Maternal leptin level increase in women who exceed 2009 GWG recommendations.

Notes: n = 8 ADHERE group; n = 9 EXCEED group. *Denotes P ≤ 0.05.
Abbreviations: GWG, gestational weight gain; IOM, Institute of Medicine.

Figure 3 Maternal leptin levels positively correlate with (A) excessive GWG and (B) HOMA-IR.

Notes: Leptin (n = 20); % exceed upper limit of gestational weight gain (GWG) target recommendation based on prepregnancy body mass index; HOMA-IR (n = 14), homeostasis model of assessment for insulin resistance; Bonferroni adjustment for multiple comparisons P ≤ 0.01.

Table 2 Maternal and fetal outcome variables for mothers who adhere to (ADHERE) and exceed (EXCEED) GWG recommendations

Maternal endpoints	GWG ADHERE	GWG EXCEED
IGF-I exp (log % IC)	2.32 (0.1)	2.24 (0.1)
IGF-II exp (log % IC)	3.03 (0.3)	2.95 (0.2)
IGFBP-1 exp (log % IC)	2.09 (0.1)	2.1 (0.1)
IGFBP-3 exp (log % IC)	1.95 (0.2)	2.16 (0.3)*
IGFBP-4 exp (log % IC)	2.22 (0.1)	2.08 (0.1)
Maternal insulin (log pg/mL)	2.67 (0.1)	2.81 (0.3)
Glucose (mmol/L)	3.68 (0.5)	4.10 (0.4)
Leptin (pg/mL)	16,659.50 (11,300.0)	29,560.33 (16,119.8)*
Fetal endpoints
IGF-I exp (log % IC)	1.87 (0.2)	1.67 (0.3)
IGF-II exp (log % IC)	1.92 (0.1)	1.92 (0.0)
IGFBP-1 exp (log % IC)	1.95 (0.1)	2.02 (0.1)
IGFBP-3 exp (log % IC)	2.23 (0.2)	2.19 (0.1)
IGFBP-4 exp (log % IC)	2.11 (0.2)	2.04 (0.1)
Cord insulin (log pg/mL)	2.61 (0.3)	2.83 (0.2)
Glucose (mmol/L)	3.56	3.01 (0.1)
Leptin (pg/mL)	182,70.71 (12319.1)	25,837.75 (18,038.3)

Notes: Data presented mean (standard deviation).

* Denotes P ≤ 0.05.

Abbreviations: IGF, insulin-like growth factor; exp, protein expression relative to IC; GWG, gestational weight gain; IC, internal control; IGFBP, insulin-like growth factor binding protein.

Table 3 Spearman correlations between maternal and fetal outcomes

Spearman correlations	% exceed GWG	Maternal leptin	HOMA-IR	Maternal IGFBP-4 expression	Birth weight
% exceed GWG		*0.64	***0.58	***0.44	**0.47
Maternal leptin (pg/mL)			*0.81	−0.21	0.33
HOMA-IR (log)				−0.31	0.14
Maternal IGFBP-4 expression (log % IC)					−0.20
Birth weight (g)

Notes: Significant correlations following Bonferroni adjustment for multiple comparisons

* P ≤ 0.01 (ie, 5/0.05 = 0.01). Significant trends were identified when P < 0.05 prior to adjustment and P = 0.01–0.05 postadjustment. Therefore,

** P = 0.02

*** P ≤ 0.05 for trend post-Bonferroni adjustment.

Abbreviations: HOMA-IR, homeostasis model of assessment for insulin resistance; IC, internal control; IGFBP-4, insulin-like growth factor binding protein-4; % exceed GWG, percent exceed upper limit for gestational weight gain based on prepregnancy body mass index.