Circulating anti-angiogenic factors during hypertensive pregnancy and increased risk of respiratory distress syndrome in preterm neonates

Figures & data

Table I.  Maternal characteristics at study enrollment for women with delivery <37 weeks in normotensive or hypertensive pregnancies.

	Normotensive (n = 323)	Hypertensive (n = 116)	p value
Age (years)	20.8 ± 4.8*	20.3 ± 3.8	NS
Weight (kg)	65.7 ± 15.4	69.9 ± 19.5	0.04
BMI	25.1 ± 5.5	27 ± 7.7	0.02
SBP (mm Hg)	105.8 ± 8.4	109.2 ± 8.9	<0.001
DBP (mm Hg)	58.9 ± 7.8	63.2 ± 8.1	<0.001
GA at enrollment (days)	122.4 ± 17.6	120.7 ± 17.8	NS
Current smoker	39 (12.1%)	7 (6.0%)	NS
Previous pregnancy	100 (31.0%)	26 (22.4%)	NS
Race/ethnicity
White, non-Hispanic	83 (25.7%)	26 (22.4%)
White, Hispanic	50 (15.5%)	15 (12.9%)	NS
Black	184 (57.0%)	70 (60.3%)
Other, unknown	6 (1.9%)	5 (4.3%)
Calcium treatment	166 (51.4%)	62 (53.5%)	NS

*Data are presented as mean ± SD or N (%). Hypertensive = preeclampsia or gestational hypertension; Calcium treatment = assigned to receive supplemental calcium; BMI, body-mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; GA, gestational age; NS, not significant.

Table II.  Perinatal outcomes for women with delivery <37 weeks in normotensive or hypertensive pregnancies.

	Normotensive (n = 323)	Hypertensive (n = 116)	p value
GA at delivery (weeks)	33.2 ± 4.3*	34.3 ± 3.0	0.002^±
Cesarean section	42 (13.0%)	38 (32.8%)	<0.001^±
Neonatal death	13 (4.4%)	2 (1.8%)	NS
Birth weight (g)	2080 ± 788	2038 ± 640	NS
SGA	18 (6.1%)	32 (28.3%)	<0.001^±
Male	178 (55.1%)	60 (52.2%)	NS
Respiratory distress syndrome	62 (20.9%)	25 (22.5%)	NS^±/0.03^†
Intraventricular hemorrhage	21 (7.1%)	5 (4.5%)	NS^±/NS^†
Necrotizing enterocolitis	5 (1.7%)	1 (0.9%)	NS^±/NS^†

*Data are presented as mean ± SD or N (%). Hypertensive = preeclampsia or gestational hypertension; GA, gestational age; SGA, small for gestational age; NS, not significant. ^±Indicates significance without adjustment. ^†Indicates significance with adjustment for gestational age at delivery.

Table III.  Comparison of serum concentrations of sFlt1, PlGF, and sEng among normotensive women who delivered preterm infants with or without respiratory distress syndrome, in specimens collected at 10–20 or 21–32 weeks.

	RDS	No RDS	p value
Collected at 10–20 weeks
Number of women	25	111
GA at collection (weeks)	17.0 ± 0.5*	16.2 ± 0.2	NS^±
GA at delivery (weeks)	29.4 ± 0.8	34.7 ± 0.3	<0.001^±
Cesarean section	6 (24.0%)	10 (9.0%)	NS^±/NS^†
Birth weight (g)	1404 ± 137	2315 ± 55	<0.001^±/NS^†
SGA	0 (0.0%)	8 (7.2%)	NS^±/NS^†
sFlt1 (pg/mL)	3895 ± 494	3542 ± 177	NS^±/NS^†
PlGF (pg/mL)	207 ± 32	146 ± 12	0.05^±/NS^†
sEng (ng/mL)	6.30 ± 1.0	5.45 ± 0.1	NS^±/NS^†
Collected at 21–32 weeks
Number of women	14	117
GA at collection (weeks)	26.5 ± 0.5	27.1 ± 0.1	NS^±
GA at delivery (weeks)	32.1 ± 0.9	35.2 ± 0.2	0.005^±
Cesarean section	3 (21.4%)	11 (9.4%)	NS^±/NS^†
Birth weight (g)	1865 ± 169	2410 ± 42	<0.001^±/NS^†
SGA	0 (0.0%)	8 (6.8%)	NS^±/NS^†
sFlt1 (pg/mL)	3645 ± 504	4430 ± 222	NS^±/NS^†
PlGF (pg/mL)	491 ± 63	706 ± 59	NS^±/NS^†
sEng (ng/mL)	5.32 ± 0.3	5.67 ± 0.2	NS^±/NS^†

*Data are presented as mean ± SD or N (%). RDS, respiratory distress syndrome; GA, gestational age; SGA, small for gestational age; sFlt1, soluble fms-like tyrosine kinase 1; PlGF, placental growth factor; sEng, soluble endoglin. ^±Indicates significance without adjustment. ^†Indicates significance with adjustment for gestational age at delivery.

Table IV.  Comparison of serum concentrations of sFlt1, PlGF and sEng among hypertensive women who delivered preterm infants with or without respiratory distress syndrome, in specimens collected at 10–20 or 21–32 weeks.

	RDS	No RDS	p value
Collected at 10–20 weeks
Number of women	18	55
GA at collection (weeks)	15.9 ± 0.6*	16.1 ± 0.4	NS^±
GA at delivery (weeks)	31.2 ± 0.8	35.4 ± 0.2	<0.001^±
Cesarean section	12 (66.7%)	11 (20%)	<0.001^±/NS^†
Birth weight (g)	1410 ± 155	2207 ± 64	<0.001^±/NS^†
SGA	8 (44.4%)	17 (30.9%)	NS^±/NS^†
sFlt1 (pg/mL)	4841 ± 1081	3216 ± 214	0.03^±/NS^†
PlGF (pg/mL)	108 ± 33	115 ± 14	NS^±/NS^†
sEng (ng/mL)	8.31 ± 1.9	6.61 ± 0.4	NS^±/NS^†
Collected at 21–32 weeks
Number of women	17	53
GA at collection (weeks)	27.9 ± 0.5	27.6 ± 0.2	NS
GA at delivery (weeks)	31.6 ± 0.8	35.2 ± 0.2	<0.001^±
Cesarean section	11 (64.7%)	11 (20.8%)	<0.001^±/NS^†
Birth weight (g)	1420 ± 156	2201 ± 75	<0.001^±/NS^†
SGA	9 (52.9%)	15 (28.3%)	NS^±/0.045^†
sFlt1 (pg/mL)	21516 ± 3734	6998 ± 674	<0.001^±/0.01^†
PlGF (pg/mL)	215 ± 136	344 ± 56	0.002^±/NS^†
sEng (ng/mL)	30.63 ± 5.7	16.07 ± 2.6	0.003^±/NS^†

*Data are presented as mean ± SD or N (%). Hypertensive = preeclampsia or gestational hypertension; RDS, respiratory distress syndrome; GA, gestational age; SGA, small for gestational age; sFlt1, soluble fms-like tyrosine kinase 1; PlGF, placental growth factor; sEng, soluble endoglin. ^±Indicates significance without adjustment. ^†Indicates significance with adjustment for gestational age at delivery.

Figure 1.  Maternal serum concentrations of sFlt1 (pg/ml) in specimens collected at 21–32 weeks of gestation in women with preeclampsia/gestational hypertension by gestational age at collection (days) and according to whether neonates did or did not develop respiratory distress syndrome (RDS).