Subgroup Analysis in Wome

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Avriam A, Berger H, Abdulaziz KE, Barrett JFR, Murray-Davis B, McDonald SD, et al. Outcomes associated with hypertensive disorders of pregnancy in twin compared with singleton gestations. Obstet Gynecol 2021;138.

The authors provided this information as a supplement to their article.

Appendix 1. Association Between Plurality and the Incidence of Hypertensive Disorders of Pregnancy – Subgroup Analysis in Women With Complete Data

Hypertensive disorder Incidence of hypertensive disorder [n (%)]

Risk of hypertensive disorders of pregnancy in twins (using singletons as reference)

Singletons N = 917,542

Twins N = 14,676

Crude RR (95% CI) Adjusted RR (95% CI)^a

Any hypertensive disorder 59,175 (6.4) 2,120 (14.4) 2.17 (2.08, 2.25) 1.86 (1.77, 1.95) Preeclampsia 37,912 (4.1) 1,428 (9.7) 2.3 (2.19, 2.42) 1.91 (1.78, 2.04) Early onset preeclampsia 2,148 (0.2) 195 (1.3) 5.64 (4.88, 6.52) 4.54 (3.58, 5.50) RR, relative risk; CI, confidence interval.

Significant associations are emphasized in bold font.

a Values reflect the results of modified Poisson regression model using women with singleton gestations as reference. Models are adjusted for maternal age, nulliparity, maternal pre-pregnancy BMI, preexisting and gestational diabetes, pre-existing hypertension, smoking, and fertility treatments. Adjusted models use only complete data.

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Appendix 2. Association of Hypertensive Disorders With Adverse Outcomes in the Singletons and Twins Groups – Subgroup Analysis in Women With Complete Data

Outcome Singletons Twins Relative risk

ratio (95%-CI)^b Incidence of outcome

[n (%)]

Relative risk (No HDP as reference)

Incidence of outcome [n (%)]

Relative risk (No HDP as reference)

No HDP N = 858,367

HDP N = 59,175

Crude RR (95% CI)

Adjusted RR (95%

CI)^a

No HDP N = 12,556

HDP N = 2,120

Crude RR (95%

CI)

Adjusted RR (95%

CI)^a

Placental abruption

9,386 (1.1)

993 (1.7) 1.54 (1.44, 1.64)

1.55 (1.43, 1.67)

234 (1.9) 30 (1.4) 0.76 (0.52, 1.11)

0.66 (0.27, 1.06)

0.43 (0.21, 0.85)

Cesarean delivery 233,510 (27.2)

23,691 (40)

1.33 (1.32, 1.34)

1.17 (1.15, 1.19)

7,527 (59.9)

1,450 (68.4)

1.14 (1.1, 1.18)

1.05 (1.00, 1.11)

0.90 (0.85, 0.95)

Maternal ICU admission

1,359 (0.2)

795 (1.3) 8.47 (7.76, 9.25)

7.01 (6.21, 7.82)

60 (0.5) 65 (3.1) 6.41 (4.53, 9.08)

4.83 (1.62, 8.05)

0.69 (0.31, 1.55)

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Maternal death 34 (0) 7 (0) 2.99 (1.32, 6.74)

N/A 0 (0.0) 0 (0.0) N/A N/A N/A

PTB<37 weeks 46,169 (5.4)

8,999 (15.2)

2.78 (2.72, 2.84)

2.43 (2.37, 2.50)

6,328 (50.4)

1,432 (67.5)

1.34 (1.29, 1.39)

1.29 (1.24, 1.35)

0.53 (0.50, 0.56)

PTB<34 weeks 9,602 (1.1)

2,530 (4.3) 3.8 (3.64, 3.97)

3.05 (2.86, 3.25)

1,697 (13.5)

253 (11.9) 0.88 (0.78, 1.00)

0.72 (0.60, 0.84)

0.24 (0.20, 0.28)

PTB<32 weeks 5,121 (0.6)

1,340 (2.3) 3.78 (3.56, 4.01)

2.78 (2.51, 3.05)

799 (6.4) 83 (3.9) 0.62 (0.49, 0.77)

0.43 (0.27, 0.60)

0.15 (0.10, 0.23)

Neonatal outcomes ^c Birth weight

<10th rcentile^d

78,077 (9.1)

8,653 (14.6)

1.61 (1.58, 1.64)

1.72 (1.68, 1.76)

6,271 (25) 1,054 (24.9)

1 (0.94, 1.06)

0.99 (0.93, 1.06)

0.58 (0.54, 0.62) 5-Minute Apgar

<7

13,059 (1.5)

2,085 (3.5) 2.31 (2.21, 2.42)

1.80 (1.70, 1.91)

974 (3.9) 216 (5.1) 1.31 (1.13, 1.51)

1.16 (0.93, 1.39)

0.64 (0.52, 0.79)

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Umbilical artery pH<7.1

13,994 (1.6)

1,494 (2.5) 1.52 (1.44, 1.6)

1.24 (1.17, 1.32)

498 (2) 95 (2.2) 1.12 (0.90, 1.39)

0.96 (0.69, 1.23)

0.77 (0.58, 1.04)

Neonatal death 926 (0.1) 106 (0.2) 1.66 (1.36, 2.03)

1.15 (0.82, 1.49)

171 (0.7) 24 (0.6) 0.83 (0.54, 1.27)

0.55 (0.23, 0.87)

0.48 (0.23, 0.99)

Admission to NICU

96,012 (11.2)

14,858 (25.1)

2.24 (2.21, 2.28)

1.83 (1.79, 1.87)

13,190 (52.5)

2,821 (66.5)

1.27 (1.24, 1.3)

1.21 (1.18, 1.25)

0.66 (0.64, 0.69)

Respiratory morbidity^e

74,516 (8.7)

9,631 (16.3)

1.87 (1.84, 1.91)

1.51 (1.48, 1.55)

8,217 (32.7)

1,687 (39.8)

1.22 (1.17, 1.27)

1.11 (1.05, 1.17)

0.74 (0.69, 0.78)

HDP, hypertensive disorders of pregnancy (gestational hypertension or preeclampsia); RR, relative risk; CI, confidence interval; ICU, intensive care unit; PTB, preterm birth; NICU, neonatal intensive care unit; N/A, non-applicable.

Significant associations are emphasized in bold font.

a Values reflect the results of modified Poisson regression analysis using women without HDP as reference. Models were adjusted for maternal age, nulliparity, maternal pre-pregnancy BMI, pre-existing and gestational diabetes, pre-existing hypertension, smoking, and fertility treatments. Adjusted models use only complete data.

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b Refers to the ratio between the RR for adverse outcome in the Twins group and the RR for adverse outcome in the singleton group.

Thus, a relative risk ratio <1.0 indicates that the association of HDP with adverse outcome is lower in twin compared with singleton gestations, while a relative risk ratio >1.0 indicates the opposite.

c The unit of analysis for neonatal outcomes in the twin group is neonate rather than pregnancies (N=25,112 for Twins-No-HDP group, and N=4,240 for the Twins-HDP group).

d Based on a Canadian birthweight-based reference of Kramer et al.²⁹ for singleton gestations, and the twins-specific standard of Grantz et al.³⁹ for twin gestations.

e Respiratory morbidity was defined as any of the following: need for respiratory support in the form of continuous positive airway pressure or mechanical ventilation, a diagnosis of transient tachypnea of the newborn or respiratory distress syndrome.