Association between pre-pregnancy body mass index and the risk of preterm birth: a mediating effect of hypertensive disorders of pregnancy

Figures & data

Figure 1. Flow chart of the participants screening.

Table 1. Characteristics of singleton pregnancies women with live births.

Variables	Total(n = 3,249,159)	Non-PTB (n = 2,924,532)	PTB (n = 324,627)	Statistics	p
Maternal age, years, Mean ± SD	29.28 ± 5.65	29.27 ± 5.61	29.41 ± 6.04	t = −12.88	<.001
Mother’s race, n (%)				χ^2 = 12,366.24	<.001
White	2,399,499 (73.85)	2,180,448 (74.56)	219,051 (67.48)
Black	502,519 (15.47)	430,680 (14.73)	71,839 (22.13)
Others (including multi-race)	347,141 (10.68)	313,404 (10.72)	33,737 (10.39)
Mother’s education level, n (%)				χ^2 = 14,971.49	<.001
11th grade or less (includes 12th grade with no diploma)	349,738 (10.76)	302,821 (10.35)	46,917 (14.45)
High school graduate or GED completed	852,858 (26.25)	753,770 (25.77)	99,088 (30.52)
Some college credit or associate degree (AA, AS)	893,670 (27.50)	802,873 (27.45)	90,797 (27.97)
Bachelor’s degree (BA, AB, BS) or above	1,111,169 (34.20)	1,028,058 (35.15)	83,111 (25.60)
Unknown	41,724 (1.28)	37,010 (1.27)	4714 (1.45)
Marital status, n (%)				χ^2 = 13,360.06	<.001
Married	1,723,513 (53.04)	1,575,490 (53.87)	148,023 (45.60)
Unmarried	1,138,997 (35.06)	995,388 (34.04)	143,609 (44.24)
Unknown	386,649 (11.90)	353,654 (12.09)	32,995 (10.16)
Father’s race, n (%)				χ^2 = 17,239.46	<.001
White	1,970,657 (60.65)	1,803,250 (61.66)	167,407 (51.57)
Black	398,222 (12.26)	347,076 (11.87)	51,146 (15.76)
Other (including multi-race)	276,200 (8.50)	251,755 (8.61)	24,445 (7.53)
Unknown	604,080 (18.59)	522,451 (17.86)	81,629 (25.15)
Father’s education level, n (%)				χ^2 = 20,048.13	<.001
11th grade or less (includes 12th grade with no diploma)	326,824 (10.06)	288,055 (9.85)	38,769 (11.94)
High school graduate or GED completed	846,050 (26.04)	755,653 (25.84)	90,397 (27.85)
Some college credit or associate degree (AA, AS)	719,407 (22.14)	653,711 (22.35)	65,696 (20.24)
Bachelor’s degree (BA, AB, BS) or above	907,535 (27.93)	842,464 (28.81)	65,071 (20.04)
Unknown	449,343 (13.83)	384,649 (13.15)	64,694 (19.93)
Smoking before pregnancy, n (%)				χ^2 = 4464.248	<.001
No smoking	3,015,075 (92.80)	2,723,174 (93.11)	291,901 (89.92)
Smoking	224,546 (6.91)	193,154 (6.60)	31,392 (9.67)
Unknown	9538 (0.29)	8204 (0.28)	1334 (0.41)
Smoking during pregnancy, n (%)				χ^2 = 58,252.13	<.001
No smoking	3,054,575 (94.01)	2,767,891 (94.64)	286,684 (88.31)
Smoking	174,951 (5.38)	148,546 (5.08)	26,405 (8.13)
Unknown	19,633 (0.60)	8095 (0.28)	11,538 (3.55)
GWG, n (%)				χ^2 = 18,574.61	<.001
Below IOM guidelines	700,749 (21.57)	601,539 (20.57)	99,210 (30.56)
Within IOM guidelines	1,014,422 (31.22)	916,156 (31.33)	98,266 (30.27)
Above IOM guidelines	1,533,988 (47.21)	1,406,837 (48.10)	127,151 (39.17)
WG, pounds, M (Q1, Q3)	29.00 (20.00, 38.00)	29.00 (20.00, 38.00)	25.00 (16.00, 35.00)	Z = −146.692	<.001
Timing of initiation of prenatal care, n (%)				χ^2 = 19,561.71	<.001
No prenatal care	53,012 (1.63)	40,734 (1.39)	12,278 (3.78)
1st to 3rd month	2,501,044 (76.98)	2,276,809 (77.85)	224,235 (69.07)
4th to 6th month	510,314 (15.71)	445,250 (15.22)	65,064 (20.04)
7th to final month	133,854 (4.12)	118,815 (4.06)	15,039 (4.63)
Unknown	50,935 (1.57)	42,924 (1.47)	8011 (2.47)
Prenatal care visits for this pregnancy, n (%)				χ^2 = 11,868.80	<.001
No visits	53,012 (1.63)	40,734 (1.39)	12278 (3.78)
1 or more visits	3,137,226 (96.56)	2,833,405 (96.88)	303,821 (93.59)
Unknown	58,921 (1.81)	50,393 (1.72)	8528 (2.63)
BMI, kg/m^2, Mean ± SD	27.33 ± 6.65	27.26 ± 6.59	27.90 ±7.11	t = −48.57	<.001
BMI level, n (%)				χ^2 = 1378.232	<.001
Under weight or normal	1,416,249 (43.59)	1,284,701 (43.93)	131,548 (40.52)
Overweight or obesity	1,832,910 (56.41)	1,639,831 (56.07)	193,079 (59.48)
Multipara, n (%)				χ^2 = 559.030	<.001
No	1,258,135 (38.72)	1,138,659 (38.93)	119,476 (36.80)
Yes	1,991,024 (61.28)	1,785,873 (61.07)	205,151 (63.20)
GDM, n (%)				χ^2 = 2032.752	<.001
No	3,002,598 (92.41)	2,709,059 (92.63)	293539 (90.42)
Yes	246,561 (7.59)	215,473 (7.37)	31,088 (9.58)
Pre-pregnancy DM, n (%)				χ^2 = 5949.588	<.001
No	3,220,242 (99.11)	2,902,420 (99.24)	317,822 (97.90)
Yes	28,917 (0.89)	22,112 (0.76)	6805 (2.10)
Gestational hypertension, n (%)				χ^2= 32,265.84	<.001
No	2,974,821 (91.56)	2,704,600 (92.48)	270,221 (83.24)
Yes	274,338 (8.44)	219,932 (7.52)	54,406 (16.76)
Eclampsia, n (%)				χ^2 = 4812.843	<.001
No	3,240,986 (99.75)	2,919,054 (99.81)	321,932 (99.17)
Yes	8173 (0.25)	5478 (0.19)	2695 (0.83)
Previous PTB, n (%)				χ^2 = 35,514.93	<.001
No	3,135,524 (96.50)	2,840,965 (97.14)	294,559 (90.74)
Yes	113,635 (3.50)	83,567 (2.86)	30,068 (9.26)
Previous cesarean, n (%)				χ^2 = 3508.962	<.001
No	2,749,458 (84.62)	2,486,308 (85.02)	263,150 (81.06)
Yes	499,701 (15.38)	438,224 (14.98)	61,477 (18.94)
Final route and method of delivery, n (%)				χ^2 = 23,185.75	<.001
Spontaneous	2,166,631 (66.68)	1,983,757 (67.83)	182,874 (56.33)
Forceps or vacuum	101,470 (3.12)	95,098 (3.25)	6372 (1.96)
Cesarean	980,118 (30.17)	844,830 (28.89)	135,288 (41.67)
Unknown	940 (0.03)	847 (0.03)	93 (0.03)
ART, n (%)				χ^2 = 492.299	<.001
No	3211742 (98.85)	2,892,133 (98.89)	319,609 (98.45)
Yes	37,417 (1.15)	32,399 (1.11)	5018 (1.55)

t: test, Z: rank sum test, χ²: chi-square test.

PTB: preterm birth; SD: standard deviation; GWG: gestational weight gain; WG: weight gain; GDM: gestational diabetes mellitus; DM: diabetes mellitus; IOM: 2009 Institute of Medicine guidelines; M: median; Q₁: 1st quartile; Q₃: 3st quartile; BMI: body mass index; ART: assisted reproductive treatment.

Table 2. Covariates screening for PTB and HDP.

Variables	PTB		HDP
	OR (95% CI)	p	OR (95% CI)	p
Maternal age	1.01 (1.01–1.01)	<.001	1.01 (1.01–1.01)	<.001
Maternal age level
<30	Ref		Ref
30–35	0.92 (0.91–0.93)	<.001	0.96 (0.95–0.96)	<.001
≥35	1.17 (1.16–1.18)	<.001	1.09 (1.08–1.10)	<.001
Mother’s race
White	Ref		Ref
Black	1.66 (1.65–1.68)	<.001	1.26 (1.25–1.27)	<.001
Others (including multi-race)	1.07 (1.06–1.08)	<.001	0.82 (0.80–0.83)	<.001
Marital status
Married	Ref		Ref
Unmarried	1.54 (1.52–1.55)	<.001	1.14 (1.14–1.15)	<.001
Unknown	0.99 (0.98–1.01)	.271	0.77 (0.76–0.78)	<.001
Mother’s education level
11th grade or less (includes 12th grade with no diploma)	Ref		Ref
High school graduate or GED completed	0.85 (0.84–0.86)	<.001	1.26 (1.24–1.27)	<.001
Some college credit or associate degree (AA, AS)	0.73 (0.72–0.74)	<.001	1.41 (1.39–1.43)	<.001
Bachelor’s degree (BA, AB, BS) or above	0.52 (0.52–0.53)	<.001	1.14 (1.12–1.16)	<.001
Unknown	0.82 (0.80–0.85)	<.001	1.01 (0.97–1.05)	.581
Father’s race
White	Ref		Ref
Black	1.59 (1.57–1.60)	<.001	1.18 (1.17–1.20)	<.001
Others (including multi-race)	1.05 (1.03–1.06)	<.001	0.76 (0.74–0.77)	<.001
Unknown	1.68 (1.67–1.70)	<.001	1.04 (1.03–1.05)	<.001
Smoking before pregnancy
No smoking	Ref		Ref
Smoking	1.52 (1.50–1.54)	<.001	1.14 (1.12–1.15)	<.001
Unknown	1.52 (1.43–1.61)	<.001	1.12 (1.05–1.20)	.001
Smoking during pregnancy
No smoking	Ref		Ref
Smoking	1.72 (1.69–1.74)	<.001	1.08 (1.06–1.10)	<.001
Unknown	13.75 (13.36–14.15)	<.001	1.30 (1.24–1.36)	<.001
GWG
Below IOM guidelines	Ref		Ref
Within IOM guidelines	0.65 (0.64–0.66)	<.001	1.05 (1.04–1.07)	<.001
Above IOM guidelines	0.55 (0.54–0.55)	<.001	1.74 (1.72–1.76)	<.001
Timing of initiation of prenatal care
No prenatal care	Ref		Ref
1st to 3rd month	0.33 (0.32–0.33)	<.001	1.27 (1.23–1.32)	<.001
4th to 6th month	0.48 (0.47–0.50)	<.001	1.15 (1.11–1.19)	<.001
7th to final month	0.42 (0.41–0.43)	<.001	1.04 (1.01–1.08)	.044
Unknown	0.62 (0.60–0.64)	<.001	1.25 (1.20–1.31)	<.001
Multipara
No	Ref		Ref
Yes	1.09 (1.09–1.10)	<.001	0.60 (0.59–0.60)	<.001
Pre-pregnancy DM
No	Ref		Ref
Yes	2.81 (2.74–2.89)	<.001	3.15 (3.07–3.24)	<.001
GDM
No	Ref		Ref
Yes	1.33 (1.32–1.35)	<.001	1.97 (1.95–2.00)	<.001
Previous PTB
No	Ref		Ref
Yes	3.47 (3.42–3.52)	<.001	1.60 (1.57–1.63)	<.001
Previous cesarean
No	Ref		Ref
Yes	1.33 (1.31–1.34)	<.001	0.93 (0.92–0.94)	<.001
ART
No	Ref		Ref
Yes	1.40 (1.36–1.45)	<.001	1.53 (1.49–1.58)	<.001

PTB: preterm birth; HDP: hypertensive disorders of pregnancy; OR: odds ratio; CI: confidence interval; Ref: reference; GWG: gestational weight gain; WG: weight gain; GDM: gestational diabetes mellitus; DM: diabetes mellitus; IOM: 2009 Institute of Medicine guidelines; BMI: body mass index; ART: assisted reproductive treatment.

Table 3. Association between pre-pregnancy BMI and HDP, HDP and PTB, and pre-pregnancy BMI and PTB.

Variables	Model 1		Model 2		Model 3
	OR (95% CI)	p	OR (95% CI)	p	OR (95% CI)	p
Pre-pregnancy BMI and HDP
BMI level
Underweight or normal	Ref		Ref
Overweight or obesity	2.33 (2.31–2.35)	<.001	2.10 (2.08–2.12)	<.001
HDP and PTB
HDP
No	Ref		Ref
Yes	2.54 (2.52–2.57)	<.001	2.56 (2.53–2.59)	<.001
Pre-pregnancy BMI and PTB
BMI level
Underweight or normal	Ref		Ref		Ref
Overweight or obesity	1.15 (1.14–1.16)	<.001	1.11 (1.10–1.12)	<.001	1.04 (1.03–1.05)	<.001

BMI: body mass index; HDP: hypertensive disorders of pregnancy; PTB: preterm birth; OR: odds ratio; CI: confidence interval; Ref: reference.

Model 1: crude model.

Model 2: adjusted for maternal age, mother’s race, mother’s educational level, marital status, father’s race, father’s educational level, smoking, GWG, GDM, pre-pregnancy DM, previous PTB, previous cesarean, ART, timing of prenatal care initiation, and multipara.

Model 3: adjusted for maternal age, mother’s race, mother’s educational level, marital status, father’s race, smoking, GWG, GDM, pre-pregnancy DM, previous PTB, previous cesarean, ART, timing of prenatal care initiation, multipara, and HDP.

Figure 2. Mediation structural model of the effect of HDP on the association between pre-pregnancy BMI and the risk of PTB.

Table 4. The mediating effect of HDP on the relationship between pre-pregnancy BMI and PTB.

Effect	Estimate (95% CI)^a	p
TE	1.12 (1.11–1.13)	<.001
CDE	1.05 (1.04–1.05)	<.001
NDE	1.04 (1.03–1.05)	<.001
NIE	1.07 (1.07–1.07)	<.001
Total risk	0.12 (0.11–0.13)	<.001
CDE risk	0.04 (0.03–0.05)	<.001
NDE risk	0.04 (0.03–0.05)	<.001
NIE risk	0.07 (0.07–0.08)	<.001
Mediation	63.62% (59.12–68.11)	<.001
Interaction	−0.36 (−4.99 to 4.27)	.879
Eliminated	63.44 (58.73–68.15)	<.001

HDP: hypertensive disorders of pregnancy; BMI: body mass index; PTB: preterm birth; CI: confidence interval; TE: total effect; CDE: controlled direct effect; NDE: natural direct effect; NIE: natural indirect effect.

The mediating effect of HDP was adjusted for maternal age, mother’s race, mother’s education level, marital status, father’s race, smoking, GWG, GDM, pre-pregnancy DM, previous PTB, previous cesarean section, ART, timing of initiation of prenatal care, and multipara.

^aEstimates for TE, CDE, NDE, and NIE represent effect values; estimates for total risk, CDE risk, NDE risk, and NIE risk represent excess relative risk; and estimates for mediation, interaction, and elimination represent proportion estimation.

Table 5. Mediating effect of HDP on the association between pre-pregnancy BMI and the risk of PTB in age and GDM subgroups.

Subgroups	Estimate (95% CI)a	p	Estimate (95% CI)	p
Age^b	Age <35 years old		Age ≥35 years old
TE	1.09 (1.08–1.10)	<.001	1.22 (1.20–1.24)	<.001
CDE	1.02 (1.01–1.03)	<.001	1.15 (1.13–1.17)	<.001
NDE	1.02 (1.01–1.03)	<.001	1.14 (1.11–1.16)	<.001
NIE	1.07 (1.07–1.07)	<.001	1.07 (1.07–1.08)	<.001
Proportion of mediation	76.78 (69.32–84.25)	<.001	38.53 (35.06–42.00)	<.001
Proportion of interaction	1.02 (−5.25 to 7.29)	.750	−2.84 (−8.90 to 3.22)	.358
Proportion of eliminated	77.30 (69.68–84.91)	<.001	37.12 (32.82–41.43)	<.001
GDM^c	No		Yes
TE	1.11 (1.10–1.12)	<.001	1.19 (1.15–1.22)	<.001
CDE	1.05 (1.04–1.06)	<.001	1.07 (1.04–1.11)	<.001
NDE	1.04 (1.03–1.05)	<.001	1.07 (1.03–1.10)	<.001
NIE	1.07 (1.07–1.07)	<.001	1.11 (1.11–1.12)	<.001
Proportion of mediation	62.38 (57.68–67.08)	<.001	64.39 (53.68–75.10)	<.001
Proportion of interaction	−1.42 (−6.27 to 3.44)	.567	3.62 (−11.04 to 18.28)	.629
Proportion of eliminated	61.67 (56.74–66.59)	<.001	66.13 (54.58–77.67)	<.001

HDP: hypertensive disorders of pregnancy; BMI: body mass index; PTB: preterm birth; CI: confidence interval; TE: total effect; CDE: controlled direct effect; NDE: natural direct effect; NIE: natural indirect effect; GDM: gestational diabetes mellitus.

^aEstimates for TE, CDE, NDE, and NIE represent effect values; estimates for total risk, CDE risk, NDE risk, and NIE risk represent excess relative risk; and estimates for mediation, interaction, and eliminated represent proportion estimation.

^bAdjusted for mother’s race, mother’s education level, marital status, father’s race, smoking, GWG, GDM, pre-pregnancy DM, previous PTB, previous cesarean section, ART, timing of initiation of prenatal care, and multipara.

^cAdjusted for maternal age, mother’s race, mother’s education level, marital status, father’s race, smoking, GWG, pre-pregnancy DM, previous PTB, previous cesarean section, ART, timing of initiation of prenatal care, and multipara.

Data availability statement

Data in this study were extracted from the National Vital Statistics System (NVSS) database. The datasets generated and/or analyzed during the current study are available in the NVSS repository, https://www.cdc.gov/nchs/nvss/index.htm.