Safety of reduced antigen content diphtheria-tetanus-acellular pertussis vaccine when administered during pregnancy as part of the maternal immunization program in Brazil: a single center, observational, retrospective, cohort study

Figures & data

Figure 1. Focus on the patient

Figure 2. Flow of participants

Notes: Exposed cohort, pregnant women who had received Tdap as part of the maternal immunization program in Brazil; unexposed Cohort, women pregnant before implementation of the maternal immunization program in Brazil who did not receive Tdap. N, number of participants.Note: Participant may have more than one elimination code assigned.^aDue to missing information (i.e., no data reported but subject number allocated).

Table 1. Demographic characteristics of study participants (total-enrolled cohort)

Characteristics	Exposed cohort N = 1203, N’ = 1199	Unexposed cohort N = 1259, N’ = 1248
Resident of the study area, n (%)	1199 (100)	1248 (100)
Age group at the beginning of pregnancy in years, n (%)
18–19 y	147 (12.3)	198 (15.9)
20–24 y	395 (32.9)	365 (29.2)
25–29 y	301 (25.1)	311 (24.9)
30–34 y	201 (16.8)	222 (17.8)
35–39 y	124 (10.3)	120 (9.6)
≥40 y	31 (2.6)	32 (2.6)
Age at the beginning of pregnancy in years, Mean (SD)	26.49 (6.15)	26.28 (6.24)

Abbreviations: N, total number of participants; N’, number of participants with data available; n (%), number (percentage) of participants; SD, standard deviation.

Table 2. Cumulative incidence of pregnancy-related adverse events and neonatal AEs of interest in current pregnancy in the exposed and unexposed cohorts (total-enrolled cohort)

	Exposed cohort N = 1199		Unexposed cohort N= 1259
Adverse event or birth outcome	n	Incidence proportion per 1000 (99% CI)	n	Incidence proportion per 1000 (99% CI)
Gestational diabetes	10	8.34 (3.10; 17.85)	22	17.47 (9.37; 29.56)
Pregnancy-related hypertension^a	11	9.17 (3.60; 19.00)	31	24.62 (14.72; 38.47)
Pre-Eclampsia	10	8.34 (3.10; 17.85)	30	23.83 (14.11; 37.50)
Eclampsia	2	1.67 (0.09; 7.73)	0	0.00 (0.00; 4.21)
HELLP Syndrome	0	0.00 (0.00; 4.42)	1	0.79 (0.00; 5.90)
Vaginal hemorrhage	4	3.34 (0.56; 10.50)	19	15.09 (7.66; 26.52)
Preterm birth	64	53.38 (37.76; 73.09)	121	96.11 (75.10; 120.99)
Small for gestational age	69	57.55 (41.27; 77.92)	62	49.25 (34.63; 67.77)

Abbreviations: CI, confidence interval; N, number of participants at risk (unexposed cohort) and with vaccination date (exposed cohort); n, number of participants where at least one event that occurred (1) between index date and date of delivery for pregnancy-related adverse events and (2) after index date for birth outcome events (preterm birth and small for gestational age). Vaginal hemorrhage includes ante-partum, intra-partum, and post-partum hemorrhage.

Note: ^aIn the total cohort, 146 pregnant women (93 in the exposed cohort and 53 in the unexposed cohort) experienced gestational or pregnancy-related hypertension independently of pre-eclampsia or eclampsia recorded in the free text variable of the electronic case report form.

Table 3. Estimated coefficients for the adjusted logistic regression model to explore the risk factors of pregnancy-related AEs and neonatal AEs of interest in current pregnancy (Total cohort)

Characteristic		Compared levels	Coefficient	Standard error	P-value	Adjusted OR (95% CI)
Gestational diabetes
Independent factor		Continuous*	−4.2961	0.2442	<.0001
Placenta abruption		Yes vs. No	2.3502	1.0966	0.0321	10.487 (1.223; 89.966)
Gestational diabetes in previous pregnancy		Yes vs. No	2.4243	0.7978	0.0024	11.294 (2.364; 53.948)
Pregnancy-related hypertension
Independent factor		Continuous*	−4.3470	0.2516	<.0001
Pre-eclampsia in previous pregnancy		Yes vs. No	1.7569	0.6493	0.0068	5.795 (1.623; 20.687)
Premature rupture of membranes in previous pregnancy		Yes vs. No	2.1498	1.0837	0.0473	8.583 (1.026; 71.793)
Vaginal hemorrhage
Independent factor		Continuous*	−4.2397	0.3464	<.0001
Tdap maternal vaccination during pregnancy		Exposed vs. Unexposed	−2.7016	1.1088	0.0148	0.067 (0.008; 0.590)
Placenta previa		Yes vs. No	5.5905	1.8417	0.0024	267.870 (7.249; >999.999)
Neonatal death in previous pregnancy		Yes vs. No	2.9178	0.8591	0.0007	18.501 (3.435; 99.646)
Preterm birth
Independent factor		Continuous*	−3.2547	0.3566	<.0001
Tdap maternal vaccination during pregnancy		Exposed vs. Unexposed	−0.5061	0.2756	0.0663	0.603 (0.351; 1.035)
Maternal age at the start of the pregnancy (in years)		18-19Y vs. 20-24Y	0.5188	0.6883	0.4510	1.680 (0.436; 6.474)
		25-29Y vs. 20-24Y	−0.1343	0.4530	0.7670	0.874 (0.360; 2.125)
		30-34Y vs. 20-24Y	0.6583	0.4114	0.1095	1.931 (0.862; 4.325)
		35-39Y vs. 20-24Y	1.0124	0.4300	0.0186	2.752 (1.185; 6.393)
		GE 40Y vs. 20-24Y	1.0044	0.7086	0.1564	2.730 (0.681; 10.949)
Pre-term baby (<37 weeks) in previous pregnancies		Yes vs. No	1.5389	0.2964	<.0001	4.659 (2.606; 8.330)
Small for gestational age
Independent factor		Continuous*	−3.3069	0.1811	<.0001
Smoking before and/or during pregnancy		Yes vs. No	0.8812	0.3773	0.0195	2.414 (1.152; 5.056)
Premature rupture of membranes in previous pregnancy		Yes vs. No	2.0789	0.8407	0.0134	7.996 (1.539; 41.539)
Neonatal hypoxic ischemic encephalopathy in previous pregnancy		Yes vs. No	3.3069	1.4258	0.0204	27.299 (1.669; 446.436)

Abbreviations: AE, adverse event; OR, odds ratio; 95% CI, 95% confidence interval; Y, years. *OR for continuous variables describes the effect of a difference of one unit.

Table 4. Cumulative incidence of other pregnancy-related adverse events and neonatal AEs of interest in current pregnancy in the exposed and unexposed cohorts (total-enrolled cohort)

	Exposed cohort N = 1199		Unexposed cohort N = 1259
Adverse event or birth outcome	n	Incidence proportion per 1000 (95% CI) (95% CI)	n	Incidence proportion per 1000 (95% CI)
Premature rupture of membranes	190	158.47 (136.73; 182.67)	261	207.31 (182.92; 234.04)
Preterm premature rupture of membranes	17	14.18 (8.26; 22.70)	36	28.59 (20.03; 39.59)
Premature uterine contraction	32	26.69 (18.26; 37.68)	54	42.89 (32.22; 55.96)
Neonatal death	0	0.00 (0.00; 3.08)	8	6.35 (2.74; 12.52)
Maternal death	0	0.00 (0.00; 3.08)	0	0.00 (0.00; 2.93)
Stillbirth	1	0.83 (0.02; 4.65)	6	4.77 (1.75; 10.37)
Neonatal hypoxic ischemic encephalopathy	0	0.00 (0.00; 3.08)	0	0.00 (0.00; 2.93)
Congenital anomalies	5	4.17 (1.35; 9.73)	22	17.47 (10.95; 26.46)

Abbreviations: CI, confidence interval; N, number of participants at risk (unexposed cohort) and with vaccination date in the exposed cohort; n, number of participants where at least one event occurred (1) between index date and date of delivery for pregnancy-related adverse events and (2) after index date for neonate-related events (neonatal death, stillbirth, neonatal hypoxic-ischemic encephalopathy, and congenital anomalies).

Table

AE	adverse event
CI	confidence interval
IEC	Independent Ethics Committee
OR	odds ratio
SD	standard deviation
Tdap	combined diphtheria-tetanus-acellular pertussis vaccine
UK	United Kingdom
US	United States