Association between hypertensive medication during pregnancy and risk of several maternal and neonatal outcomes in women with chronic hypertension: a population-based study

Figures & data

Figure 1. Flowchart of exclusion and inclusion criteria.

Table 1. Selected cohort characteristics of women among the exposure groups. Lombardy Region, Italy, 2007–2017.

	Unadjusted			Adjusted*
	Users	No-Users	SMD- %	Users	No-users	SMD- %
Characteristics	(N = 2138)	(N = 3415)		(N = 2134)	(N = 3413)
Maternal Covariates§
Maternal age- mean (SD), y	37 (4.6)	35 (4.8)	37.3	37 (4.6)	37 (4.5)	0.0
Diabetes – no. (%)	78 (3.6)	100 (2.9)	4	78 (3.7)	118 (3.5)	1.0
Hypothyroidisms – no. (%)	136 (6.4)	300 (8.8)	−9.2	136 (6.4)	205 (6)	1.5
Obesity or overweight – no. (%)	21 (1)	40 (1.2)	−1.8	21 (1)	33 (1)	0.3
Renal disorder – no. (%)	17 (0.8)	21 (0.6)	2.2	17 (0.8)	31 (0.9)	−1.1
Dyslipidemia – no. (%)	61 (2.9)	106 (3.1)	−1.5	61 (2.9)	102 (3)	−0.8
Substance dependence – no. (%)	4 (0.2)	7 (0.2)	−0.4	4 (0.2)	5 (0.1)	1.0
Previous preeclampsia – no. (%)	189 (8.8)	277 (8.1)	2.6	187 (8.8)	291 (8.5)	0.9
Previous gestational diabetes – no. (%)	63 (2.9)	77 (2.3)	4.3	63 (3)	101 (3)	−0.1
Previous gestational hypertension – no. (%)	133 (6.2)	204 (6)	1	133 (6.2)	224 (6.6)	−1.4
Depression – no. (%)	159 (7.4)	256 (7.5)	−0.2	158 (7.4)	261 (7.6)	−0.9
Cardiac Arrhythmia – no. (%)	8 (0.4)	22 (0.6)	−3.8	8 (0.4)	13 (0.4)	−0.3
Migraine/headache – no. (%)	4 (0.2)	12 (0.4)	−3.2	4 (0.2)	6 (0.2)	0.5
Stress, anxiety and epilepsy – no. (%)	55 (2.6)	91 (2.7)	−0.6	54 (2.5)	86 (2.5)	0.1
Socio – demographic Covariates∫
Parity
Multipar – no. (%)	1152 (53.9)	1693 (49.6)	8.6	1149 (53.8)	1811 (53)	1.6
Concomitant Medication¥
Antiplatelet- no. (%)	399 (18.7)	262 (7.7)	32.9	395 (18.5)	626 (18.3)	0.4
NSAIDs – no. (%)	303 (14.2)	348 (10.2)	12.2	301 (14.1)	473 (13.9)	0.7
Antipsychotics – no. (%)	198 (9.3)	249 (7.3)	7.2	197 (9.2)	326 (9.6)	−1.1
Regional Health System Utilization§
Drugs Prescription
≤ 1 – no. (%)	271 (12.7)	580 (17)	−12.1	271 (12.7)	447 (13.1)	−1.2
2 – no. (%)	385 (18)	656 (19.2)	−3.1	385 (18)	613 (18)	0.2
≥ 3 – no. (%)	1482 (69.3)	2179 (63.8)	11.7	1478 (69.3)	2353 (68.9)	0.7
Hospitalization
≥ 1 – no. (%)	545 (25.5)	1075 (31.5)	−13.3	545 (25.5)	860 (25.2)	0.8

Abbreviations: LMP, last menstrual period; NSAIDs, nonsteroidal anti-inflammatory drugs, SMD, standardized mean difference

* To account for propensity score, unexposed women were weighted using the distribution of the exposed women among propensity score strata.

§ Maternal covariates and healthcare utilization measured during the wash-out period (i.e. between LMP-2 years and LMP-1 year).

¥ Concomitant medication measured from the year before the LMP to the 20th gestational week.

∫ Data related to the current pregnancy.

Figure 2. Forest plot of the risk ratio for the association between antihypertensive treatment and maternal and neonatal outcomes, unadjusted and propensity score stratified adjusted analyses. Lombardy Region, Italy, 2007–2017.

Table 2. Adjusted relative risk of neonatal outcome among women without pregnancy hypertensive disorders. Lombardy, Italy, 2007–2017 (N = 4689).

	No. of Women		No. of Outcomes
	Users	No-Users	Users	No-Users	RR	(95% CI)
Low Apgar Score	1732	2957	11	14	1.58	(0.61–2.95)
Low Birth Weight	1732	2957	224	228	1.59	(1.34–1.89)
Preterm Birth	1732	2957	232	261	1.33	(1.13–1.56)

Table 3. Adjusted relative risk of maternal and neonatal outcome among recommended drug classes. Lombardy, Italy, 2007–2017.

	Antiadrenergic agents (ATC C02)					Beta Blocking Agents (ATC C07)					Calcium Channel Blockers (ATC C08)
	No. of Women		No. of Outcomes		RR (95% CI)¥	No. of Women		No. of Outcomes		RR (95% CI)¥	No. of Women		No. of Outcomes		RR (95% CI)¥
	Users	No-Users	Users	No-Users		Users	No-Users	Users	No-Users		Users	No-Users	Users	No-Users
Exacerbation of hypertension	479	4968	48	374	1.18 (0.89–1.57)	594	4911	39	382	0.85 (0.62–1.17)	1059	4480	77	349	0.85 (0.67–1.08)
Preeclampsia	479	4968	73	390	1.66 (1.32–2.09)	594	4911	44	416	0.78 (0.58–1.06)	1059	4480	157	307	1.88 (1.58–2.24)
Low Apgar Score	479	4968	6	27	2.37 (0.98–5.74)	594	4911	3	30	0.71 (0.22–2.31)	1059	4480	9	24	1.43 (0.67–3.03)
Low Birth Weight	479	4968	106	597	1.70 (1.41–2.03)	594	4911	98	608	1.22 (1.01–1.48)	1059	4480	167	541	1.12 (0.96–1.32)
Preterm Birth	479	4968	121	656	1.69 (1.43–1.99)	594	4911	83	693	0.90 (0.73–1.11)	1059	4480	205	577	1.25 (1.09–1.44)

¥ PSS adjustment included all maternal covariates and the concomitant use of recommended and unrecommended antihypertensive drugs

Figure 3. Influence of an unmeasured confounder on the relationship between use of antihypertensive treatment during the first 20 weeks of gestation, with respect to no-use, and the risk of preeclampsia, low birth weight, and preterm birth. The graph indicates the combinations of confounder‐outcome (RR_CD) and exposure‐confounder (OR_EC) associations that would be required to move the observed effect of antihypertensive treatment toward the null. Lombardy Region, Italy, 2007–2017.