Penta is associated with an increased female-male mortality ratio: cohort study from Bangladesh

Figures & data

Figure 1. Flowchart of study population

Table 1. Background characteristics of study children according to sex

Characteristics	Girls	Boys
Total number of children	3723	3921
Mean number of visits (SD) (*P = .77)	2.39(0.49)	2.39(0.49)
Median age in month of first visit (IQR) (P = .82)	3.32(1.74–5.26)	3.42(1.71–5.26)
Season of birth (P = .65)
Jan-Mar, % (N)	29%(1083)	28%(1097)
Apr-Jun, % (N)	21%(785)	22%(857)
Jul-Sep, % (N)	25%(916)	24%(956)
Oct-Dec, % (N)	25%(939)	26%(1011)
Parity (P = .09)
1, % (N)	30%(1176)	32%(1174)
2, % (N)	27%(957)	26%(1046)
3 and above, % (N)	43%(1584)	43%(1685)
Missing	0%(6)	0%(16)
Mother’s education (P = .65)
Not attended high school, %(N)	63%(2316)	62%(2470)
Attended high school, % (N)	37%(1405)	38%(1450)
Missing	0%(2)	0%(1)
Mother’s age (years) (P = .40)
<20, % (N)	16%(659)	18%(641)
20–29, % (N)	65%(2404)	65%(2567)
30 and above, % (N)	18%(658)	18%(712)
Missing	0%(2)	0%(1)

* P-values for test of no difference in background characteristics between boys and girls: (Chi square for categorical variables, t-test for mean number of visit, and Mann-Whitney for median age). IQR: interquartile range; SD: Standard deviation

Table 2. Deaths per 1000 person-years (pyrs) and female-male (F/M) mortality rate ratios (MRR) according to vaccination status in children aged 6 weeks-9 months

Group	Vaccination status*	Girls MR per 1000 pyrs (Deaths/Pyrs)N	Boys MR per 1000 pyrs (Deaths/Pyrs)N	Crude F/M MRR
	BCG-only first
I	BCG only (P = .45)	19(2/107)224	38(4/104)218	0.48(0.04–3.38)
II	BCG then Penta1	0(0/79)188	0(0/90)213	NA
III	BCG then Penta1 then Penta2 (P = .61)	25(2/80)242	11(1/88)261	2.18(0.11–128.67)
IV	BCG then Penta1 then Penta2 then Penta3 (P = .25)	19(2/107)569	0(0/110)617	NA***
	BCG and Penta1 simultaneously first
V	BCG+Penta1(P = .61)	13(2/157)367	6(1/168)398	2.14(0.11–126.57)
VI	BCG+Penta1then Penta2	0(0/134)392	0(0/142)420	NA
VII	BCG+Penta1 then Penta2 then Penta3 (P = .03)	26(5/192)978	0(0/206)1040	NA***
	Penta-only first
VIII	Penta1 only	0(0/15)39	0(0/20)48	NA
IX	Penta1 then Penta2	0(0/6)17	0(0/7)23	NA
X	Penta1 then Penta2 then Penta3	0(0/5)24	0(0/5)24	NA
XI	Penta1< BCG ** (P = .48)	30(1/33)140	0(0/37)158	NA***
	Others
	Have card but not seen (P = .49)	0(0/114)358	9(1/109)345	NA***
	Documented no vaccination (P = .39)	22(13/592)1304	15(9/615)1358	1.50(0.60–4.00)

*Vaccination status (defined as children hitherto administered vaccination sequence) updated between visits during 6 week and 9 months of age. Thus, children can contributed with follow-up time to several of the vaccination groups (I–XI). Notably, children can only contribute to one of the three broader categories: BCG-only first, BCG and Penta1 simultaneously first, or Penta1-only first. However, a child could start e.g., as unvaccinated and thus also contribute to the “Others” category. Therefore, the number of children for different overall vaccination categories in the table sum up to more than the total number of children in the study.

**Received Penta1 then BCG+Penta2; Penta1-then BCG+Penta2-then Penta3; Penta1-then Penta2-then BCG+Penta3; Penta1-then BCG; Penta1-then Penta2-then BCG;Penta1-then BCG-then Penta2-then Penta3; Penta1-then Penta2-then Penta3-then BCG.

*** Due to 0 deaths in one of the groups we were unable to calculate an MRR

NA: Not applicable

P = P-value for two-sided Fisher’s exact test

Figure 2. Mortality rate per 1000 person-years according to sex for children ages 6 weeks to 9 months. The curves have been smoothed with a weighted kernel density utilizing the estimated hazard

Table 3. Deaths per 1000 person-years (pyrs) and mortality rate ratios (MRR) according to sex and vaccination status

	Mean age in month of first visit		Mortality rate(deaths/pyrs)		Crude MRR		**Adjusted MRR
Most recent vaccine*	Girls	Boys	Girls	Boys	Girls	Boys	Girls	Boys	Crude F/M MRR	**Adjusted F/M MRR
Number of children			N = 3226	N = 3404
BCG vaccinated only (Group I) (N = 442)	2.12	2.10	18.3(2/107)	37.0(4/104)	Ref	Ref	Ref	Ref	0.48(0.09–2.64)	0.47(0.09–2.48)
Penta vaccinated ((Group II, III, IV,VI–X) (N = 4818)	5.40	5.35	14.3(9/618)	1.4(1/667)	0.78 (0.17–3.57)	0.04(0.01–0.36)	1.35(0.31–5.97)	0.07(0.01–0.76)	9.66(1.22–76.21)	9.91(1.16–84.44)
Documented no vaccination (N = 2662)	2.25	2.21	21.5(13/592)	14.4(9/615)	1.17(0.26–5.12)	0.39(0.22–1.24)	1.27(0.29–5.46)	0.36(0.11–1.15)	1.51(0.65–3.54)	1.51(0.76–3.01)

*Vaccination status (defined as children hitherto administered vaccination sequence) updated between visits during 6 week and 9 months of age. Thus, children can contributed with follow-up time to several of the vaccination groups (I–XI). Notably, children can only contribute to one of the three broader categories: BCG-only first, BCG and Penta1 simultaneously first, or Penta1-only first. However, a child could start e.g., as unvaccinated and thus also contribute to the “Documented no vaccination” category. Therefore, the number of children for different overall vaccination categories in the table sum up to more than the total number of children in the study.

** Adjusted for season of birth, parity, maternal age and education, and villages in a Cox proportional hazards model