Table 2 Open in new tab Adjusted hazard...

Outcomes	Events, no.	Crude incidence per 1000 person-years	HRs (95% CI)
Number of PL
CVD
None	1583	0.96	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	497	1.14	1.19 (1.07–1.31)	1.19 (1.08–1.32)	1.18 (1.06–1.31)
≥2	145	1.24	1.43 (1.20–1.69)	1.38 (1.16–1.64)	1.34 (1.13–1.59)
P for trend			<0.001	<0.001	<0.001
CHD
None	1070	0.65	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	324	0.74	1.14 (1.01–1.29)	1.16 (1.02–1.32)	1.15 (1.01–1.30)
≥2	104	0.89	1.53 (1.25–1.87)	1.48 (1.20–1.81)	1.44 (1.17–1.76)
P for trend			<0.001	<0.001	<0.001
Stroke
None	523	0.32	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	174	0.40	1.26 (1.06–1.50)	1.25 (1.05–1.48)	1.23 (1.03–1.47)
≥2	44	0.38	1.28 (0.94–1.75)	1.25 (0.91–1.71)	1.21 (0.88–1.65)
P for trend			0.006	0.01	0.02
Age at first PL
CVD
None	1583	0.96	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	200	0.86	0.96 (0.82–1.11)	0.99 (0.85–1.15)	1.03 (0.88–1.19)
24–29 years	241	1.18	1.27 (1.10–1.45)	1.27 (1.10–1.45)	1.25 (1.09–1.43)
≤23 years	201	1.70	1.65 (1.43–1.92)	1.53 (1.32–1.77)	1.40 (1.21–1.62)
P for trend			<0.001	<0.001	<0.001
CHD
None	1070	0.65	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	123	0.53	0.87 (0.72–1.05)	0.92 (0.76–1.11)	0.95 (0.79–1.15)
24–29 years	164	0.80	1.28 (1.09–1.51)	1.30 (1.10–1.53)	1.28 (1.08–1.51)
≤23 years	141	1.19	1.70 (1.41–2.03)	1.56 (1.30–1.86)	1.42 (1.18–1.69)
P for trend			<0.001	<0.001	<0.001
Stroke
None	523	0.32	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	80	0.34	1.15 (0.91–1.46)	1.17 (0.92–1.49)	1.20 (0.94–1.53)
24–29 years	77	0.38	1.21 (0.95–1.53)	1.19 (0.93–1.51)	1.17 (0.91–1.49)
≤23 years	61	0.52	1.55 (1.19–2.03)	1.45 (1.11–1.90)	1.36 (1.04–1.78)
P for trend			<0.001	0.003	0.01

Outcomes

Events, no.

Crude incidence per 1000 person-years

HRs (95% CI)

Age-adjusted model^a

Multivariable model 1^b

Multivariable model 2^c

Number of PL

CVD

None

1583

0.96

1.00 (reference)

497

1.14

1.19 (1.07–1.31)

1.19 (1.08–1.32)

1.18 (1.06–1.31)

≥2

145

1.24

1.43 (1.20–1.69)

1.38 (1.16–1.64)

1.34 (1.13–1.59)

P for trend

<0.001

CHD

None

1070

0.65

1.00 (reference)

324

0.74

1.14 (1.01–1.29)

1.16 (1.02–1.32)

1.15 (1.01–1.30)

≥2

104

0.89

1.53 (1.25–1.87)

1.48 (1.20–1.81)

1.44 (1.17–1.76)

P for trend

<0.001

Stroke

None

523

0.32

1.00 (reference)

174

0.40

1.26 (1.06–1.50)

1.25 (1.05–1.48)

1.23 (1.03–1.47)

≥2

0.38

1.28 (0.94–1.75)

1.25 (0.91–1.71)

1.21 (0.88–1.65)

P for trend

0.006

0.01

0.02

Age at first PL

CVD

None

1583

0.96

1.00 (reference)

≥30 years

200

0.86

0.96 (0.82–1.11)

0.99 (0.85–1.15)

1.03 (0.88–1.19)

24–29 years

241

1.18

1.27 (1.10–1.45)

1.25 (1.09–1.43)

≤23 years

201

1.70

1.65 (1.43–1.92)

1.53 (1.32–1.77)

1.40 (1.21–1.62)

P for trend

<0.001

CHD

None

1070

0.65

1.00 (reference)

≥30 years

123

0.53

0.87 (0.72–1.05)

0.92 (0.76–1.11)

0.95 (0.79–1.15)

24–29 years

164

0.80

1.28 (1.09–1.51)

1.30 (1.10–1.53)

1.28 (1.08–1.51)

≤23 years

141

1.19

1.70 (1.41–2.03)

1.56 (1.30–1.86)

1.42 (1.18–1.69)

P for trend

<0.001

Stroke

None

523

0.32

1.00 (reference)

≥30 years

0.34

1.15 (0.91–1.46)

1.17 (0.92–1.49)

1.20 (0.94–1.53)

24–29 years

0.38

1.21 (0.95–1.53)

1.19 (0.93–1.51)

1.17 (0.91–1.49)

≤23 years

0.52

1.55 (1.19–2.03)

1.45 (1.11–1.90)

1.36 (1.04–1.78)

P for trend

<0.001

0.003

0.01

Outcomes	Events, no.	Crude incidence per 1000 person-years	HRs (95% CI)
Number of PL
CVD
None	1583	0.96	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	497	1.14	1.19 (1.07–1.31)	1.19 (1.08–1.32)	1.18 (1.06–1.31)
≥2	145	1.24	1.43 (1.20–1.69)	1.38 (1.16–1.64)	1.34 (1.13–1.59)
P for trend			<0.001	<0.001	<0.001
CHD
None	1070	0.65	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	324	0.74	1.14 (1.01–1.29)	1.16 (1.02–1.32)	1.15 (1.01–1.30)
≥2	104	0.89	1.53 (1.25–1.87)	1.48 (1.20–1.81)	1.44 (1.17–1.76)
P for trend			<0.001	<0.001	<0.001
Stroke
None	523	0.32	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	174	0.40	1.26 (1.06–1.50)	1.25 (1.05–1.48)	1.23 (1.03–1.47)
≥2	44	0.38	1.28 (0.94–1.75)	1.25 (0.91–1.71)	1.21 (0.88–1.65)
P for trend			0.006	0.01	0.02
Age at first PL
CVD
None	1583	0.96	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	200	0.86	0.96 (0.82–1.11)	0.99 (0.85–1.15)	1.03 (0.88–1.19)
24–29 years	241	1.18	1.27 (1.10–1.45)	1.27 (1.10–1.45)	1.25 (1.09–1.43)
≤23 years	201	1.70	1.65 (1.43–1.92)	1.53 (1.32–1.77)	1.40 (1.21–1.62)
P for trend			<0.001	<0.001	<0.001
CHD
None	1070	0.65	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	123	0.53	0.87 (0.72–1.05)	0.92 (0.76–1.11)	0.95 (0.79–1.15)
24–29 years	164	0.80	1.28 (1.09–1.51)	1.30 (1.10–1.53)	1.28 (1.08–1.51)
≤23 years	141	1.19	1.70 (1.41–2.03)	1.56 (1.30–1.86)	1.42 (1.18–1.69)
P for trend			<0.001	<0.001	<0.001
Stroke
None	523	0.32	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	80	0.34	1.15 (0.91–1.46)	1.17 (0.92–1.49)	1.20 (0.94–1.53)
24–29 years	77	0.38	1.21 (0.95–1.53)	1.19 (0.93–1.51)	1.17 (0.91–1.49)
≤23 years	61	0.52	1.55 (1.19–2.03)	1.45 (1.11–1.90)	1.36 (1.04–1.78)
P for trend			<0.001	0.003	0.01

Table 2

Open in new tab

Adjusted hazard ratios of cardiovascular disease, coronary heart disease, and stroke according to the number of pregnancy loss and age at first pregnancy loss among 95 465 ever-gravid women (Nurses’ Health Study II, 1993–2017)

Outcomes	Events, no.	Crude incidence per 1000 person-years	HRs (95% CI)
Outcomes	Events, no.	Crude incidence per 1000 person-years	Age-adjusted model^a	Multivariable model 1^b	Multivariable model 2^c
Number of PL
CVD
None	1583	0.96	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	497	1.14	1.19 (1.07–1.31)	1.19 (1.08–1.32)	1.18 (1.06–1.31)
≥2	145	1.24	1.43 (1.20–1.69)	1.38 (1.16–1.64)	1.34 (1.13–1.59)
P for trend			<0.001	<0.001	<0.001
CHD
None	1070	0.65	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	324	0.74	1.14 (1.01–1.29)	1.16 (1.02–1.32)	1.15 (1.01–1.30)
≥2	104	0.89	1.53 (1.25–1.87)	1.48 (1.20–1.81)	1.44 (1.17–1.76)
P for trend			<0.001	<0.001	<0.001
Stroke
None	523	0.32	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	174	0.40	1.26 (1.06–1.50)	1.25 (1.05–1.48)	1.23 (1.03–1.47)
≥2	44	0.38	1.28 (0.94–1.75)	1.25 (0.91–1.71)	1.21 (0.88–1.65)
P for trend			0.006	0.01	0.02
Age at first PL
CVD
None	1583	0.96	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	200	0.86	0.96 (0.82–1.11)	0.99 (0.85–1.15)	1.03 (0.88–1.19)
24–29 years	241	1.18	1.27 (1.10–1.45)	1.27 (1.10–1.45)	1.25 (1.09–1.43)
≤23 years	201	1.70	1.65 (1.43–1.92)	1.53 (1.32–1.77)	1.40 (1.21–1.62)
P for trend			<0.001	<0.001	<0.001
CHD
None	1070	0.65	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	123	0.53	0.87 (0.72–1.05)	0.92 (0.76–1.11)	0.95 (0.79–1.15)
24–29 years	164	0.80	1.28 (1.09–1.51)	1.30 (1.10–1.53)	1.28 (1.08–1.51)
≤23 years	141	1.19	1.70 (1.41–2.03)	1.56 (1.30–1.86)	1.42 (1.18–1.69)
P for trend			<0.001	<0.001	<0.001
Stroke
None	523	0.32	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	80	0.34	1.15 (0.91–1.46)	1.17 (0.92–1.49)	1.20 (0.94–1.53)
24–29 years	77	0.38	1.21 (0.95–1.53)	1.19 (0.93–1.51)	1.17 (0.91–1.49)
≤23 years	61	0.52	1.55 (1.19–2.03)	1.45 (1.11–1.90)	1.36 (1.04–1.78)
P for trend			<0.001	0.003	0.01

Outcomes	Events, no.	Crude incidence per 1000 person-years	HRs (95% CI)
Outcomes	Events, no.	Crude incidence per 1000 person-years	Age-adjusted model^a	Multivariable model 1^b	Multivariable model 2^c
Number of PL
CVD
None	1583	0.96	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	497	1.14	1.19 (1.07–1.31)	1.19 (1.08–1.32)	1.18 (1.06–1.31)
≥2	145	1.24	1.43 (1.20–1.69)	1.38 (1.16–1.64)	1.34 (1.13–1.59)
P for trend			<0.001	<0.001	<0.001
CHD
None	1070	0.65	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	324	0.74	1.14 (1.01–1.29)	1.16 (1.02–1.32)	1.15 (1.01–1.30)
≥2	104	0.89	1.53 (1.25–1.87)	1.48 (1.20–1.81)	1.44 (1.17–1.76)
P for trend			<0.001	<0.001	<0.001
Stroke
None	523	0.32	1.00 (reference)	1.00 (reference)	1.00 (reference)
1	174	0.40	1.26 (1.06–1.50)	1.25 (1.05–1.48)	1.23 (1.03–1.47)
≥2	44	0.38	1.28 (0.94–1.75)	1.25 (0.91–1.71)	1.21 (0.88–1.65)
P for trend			0.006	0.01	0.02
Age at first PL
CVD
None	1583	0.96	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	200	0.86	0.96 (0.82–1.11)	0.99 (0.85–1.15)	1.03 (0.88–1.19)
24–29 years	241	1.18	1.27 (1.10–1.45)	1.27 (1.10–1.45)	1.25 (1.09–1.43)
≤23 years	201	1.70	1.65 (1.43–1.92)	1.53 (1.32–1.77)	1.40 (1.21–1.62)
P for trend			<0.001	<0.001	<0.001
CHD
None	1070	0.65	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	123	0.53	0.87 (0.72–1.05)	0.92 (0.76–1.11)	0.95 (0.79–1.15)
24–29 years	164	0.80	1.28 (1.09–1.51)	1.30 (1.10–1.53)	1.28 (1.08–1.51)
≤23 years	141	1.19	1.70 (1.41–2.03)	1.56 (1.30–1.86)	1.42 (1.18–1.69)
P for trend			<0.001	<0.001	<0.001
Stroke
None	523	0.32	1.00 (reference)	1.00 (reference)	1.00 (reference)
≥30 years	80	0.34	1.15 (0.91–1.46)	1.17 (0.92–1.49)	1.20 (0.94–1.53)
24–29 years	77	0.38	1.21 (0.95–1.53)	1.19 (0.93–1.51)	1.17 (0.91–1.49)
≤23 years	61	0.52	1.55 (1.19–2.03)	1.45 (1.11–1.90)	1.36 (1.04–1.78)
P for trend			<0.001	0.003	0.01

CI, confidence interval; CHD, coronary heart disease; CVD, cardiovascular disease; HRs, hazard ratios; PL, pregnancy loss.

Age in months (continuous) at the start of follow-up and calendar year of the current questionnaire cycle were included as stratified variables.

Based on the age-adjusted model, multivariable model 1 was further adjusted for White race/ethnicity (yes vs. no), parental history of myocardial infarction or stroke (yes/no), body mass index at age 18 years (<19, 20.5–21.9, 22–24.9, 25–29.9, or ≥30 kg/m²), and time-varying history of gestational diabetes (yes vs. no), hypertensive disorders of pregnancy (yes vs. no), menopausal status (premenopausal, postmenopausal, or unsure/biologically uncertain), current hormone therapy use (never, past, or current), breastfeeding duration (<3, 3–12, or >12 months), daily aspirin use (yes vs. no), infertility (never vs. ever), and marital status (ever/currently married vs. never).

Based on multivariable model 1, multivariable model 2 was further adjusted for time-varying smoking status (never, former, or current), physical activity (0, 0.1–1.0, 1.1–2.4, 2.5–5.9, or ≥6 h/week), Alternative Healthy Eating Index 2010 diet quality score (quintiles), and body mass index (<23, 23–24.9, 25–29.9, and ≥30 kg/m²).

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