Background
Women are particularly vulnerable to depression during pregnancy and childbirth which may partly be attributable to hormonal change, social factors such as luck of support, and economic deprivation for women in low income countries [
1‐
4]. Perinatal depression refers to depression occurring during pregnancy (antenatal depression) and after child birth (postnatal depression) [
5]. In Ethiopia, the prevalence of antenatal and postnatal depression has been reported in the range from 7 to 31.1% and 9 to 33.8%, respectively [
6‐
9].
Adequate provision of care for a new-born baby requires commitment and engagement [
10]. These qualities can be reduced in depression due to associated fatigue, guilt, loss of concentration, worthlessness or hopelessness [
11]. Antenatal depression is associated with a 30% risk of reduced maternal infant responsiveness [
12,
13] whilst postnatal depression has been associated with impaired growth and poor cognitive development amongst infants, particularly those in low-income countries [
14‐
16]. Infants of antenatally depressed women in low- and middle-income countries have been found to have an increased risk for early cessation of breastfeeding, stunting and underweight [
17‐
20], although these findings are equivocal [
14,
15,
20,
21].
In Ethiopia, the association between maternal common mental disorders and the risk of infant illnesses and malnutrition has been inconsistently observed [
22‐
24]. Differences in findings might potentially be due to bias as a result of unobserved confounding, which cannot be overcome using standard regression techniques [
25,
26]. Failure to account for unobserved confounding can weaken the quality of evidence derived from such studies [
27].
The current study therefore applied recently developed causal inference techniques to estimate the causal average treatment effect of perinatal depression on the risk of diarrhea, acute respiratory infection (ARI) and malnutrition in infants aged up to 6 months. We used the doubly robust semi-parametric method known as Targeted Maximum Likelihood Estimation (TMLE) [
28] which reduces the risk of bias by modelling the exposure as well as the outcome. Such models are robust to bias provided that either the exposure or the outcome model is correctly specified i.e. includes all relevant confounders. We also examined likely mediators of any causal associations.
Results
A total of 878 mother-infant dyads were followed to 6 months after birth. During follow up, two women withdrew and 10 were not contacted due to change of address leaving an overall loss-to-follow up of 1.3% and a final data set of 866 mother-infant dyads considered for analysis. We did a complete case analysis excluding the women who were lost from the cohort.
Socio-demographic characteristics
The socio-demographic characteristics of the study participants are described in Table
1. The mean (SD) age of the mothers and the infants were 26.5 (4.5) years and 4.8 (1.3) months, respectively. There was a significant age difference for infants with and without diarrhea (
p = 0.024) and malnutrition (
p = < 0.001). Nearly half of the participants (
n = 422, 48.7%) reported low-income, 322 (37.2%) completed high school, and 700 (80.8%) were Orthodox Christians. Education, income, and religion were associated with infant malnutrition and ARI (
p < 0.001 for each). Most participants were engaged in home duties (
n = 617, 71.3%), partnered (
n = 832, 96.1%), and did not have difficulties in accessing food in the previous 3 months (
n = 832, 96.1%).
Table 1
Socio-demographic characteristics of study participants according to those with and without Diarrhea, Acute Respiratory Infection (ARI), and Malnutrition in Gondar Town, Ethiopia, (n = 866)
Women age at enrolment in years | | | 0.571 | | | 0.057 | | | 0.947 |
18–24 | 45 (30.6) | 236(32.8) | | 51 (27.3) | 230(33.9) | | 39 (31.2) | 242(32.7) | |
25–34 | 89 (60.5) | 436(60.6) | | 117 (62.6) | 408(60.1) | | 77 (61.6) | 448(60.5) | |
> =35 | 13 (8.8) | 47(6.5) | | 19 (10.1) | 41(6.0) | | 9 (7.2) | 51(6.8) | |
Infant age (Mean(±SD) in months | 4.98 (1.04) | 4.73(1.29) | 0.024 | 4.82 (1.21) | 4.76(1.27) | 0.543 | 4.09 (1.41) | 4.9(1.19) | < 0.001 |
Household monthly income | | | 0.942 | | | 0.793 | | | 0.022 |
Low | 70 (47.6) | 352(49.0) | | 87 (46.5) | 335(49.3) | | 71 (56.8) | 351(47.4) | |
Medium | 61 (41.5) | 294(40.9) | | 80 (42.8) | 275(40.5) | | 49 (39.2) | 306(41.3) | |
High | 16 (10.9) | 73(10.1) | | 20 (10.7) | 69(10.2) | | 5 (4.0) | 84(11.3) | |
Women education | | | 0.201 | | | 0.091 | | | 0.028 |
None | 25 (17.0) | 86(12.0) | | 33 (17.6) | 78(11.5) | | 19 (15.2) | 92(12.4) | |
Primary | 32 (21.8) | 191(26.6) | | 43 (23.0) | 180(26.5) | | 42 (33.6) | 181(24.4) | |
High school | 50 (34.0) | 272(37.8) | | 62 (33.2) | 260(38.3) | | 45 (36.0) | 277(37.4) | |
Tertiary | 40 (27.2) | 170(23.6) | | 49 (26.2) | 161(23.7) | | 19 (15.2) | 191(25.8) | |
Women occupation | | | 0.079 | | | 0.661 | | | 0.101 |
Domestic duties | 107 (72.8) | 510(70.9) | | 133 (71.1) | 484(71.3) | | 98 (78.4) | 519(70.0) | |
Student | 4 (2.7) | 9(1.2) | | 1 (0.5) | 12(1.8) | | 2 (1.6) | 11(1.5) | |
Government employee | 25 (17.0) | 99(13.8) | | 28 (15.0) | 96(14.1) | | 9 (7.2) | 115(15.5) | |
Self-employee | 11 (7.5) | 101(14.1) | | 25 (13.4) | 87(12.8) | | 16 (12.8) | 96(13.0) | |
Women religion | | | 0.155 | | | 0.000 | | | 0.467 |
Orthodox | 125 (85.0) | 575(80.0) | | 176 (94.1) | 524(77.2) | | 104 (83.2) | 596(80.4) | |
Muslim | 22 (15.0) | 144(20.0) | | 11 (5.9) | 155(22.8) | | 21 (16.8) | 145(19.6) | |
Women marital status | | | 0.196 | | | 0.568 | | | 0.124 |
Single | 3 (2.0) | 31(4.3) | | 6 (3.2) | 28(4.1) | | 8 (6.4) | 26(3.5) | |
Partnered | 144 (98.0) | 688(95.7) | | 181 (96.8) | 651(95.9) | | 117 (93.6) | 715(96.5) | |
Difficulty accessing food in the last three months | 0.299 | | | 0.258 | | | 0.124 |
Yes | 8 (5.4) | 26(3.6) | | 10 (5.3) | 24(3.5) | | 8 (6.4) | 26(3.5) | |
No | 139 (94.6) | 693(96.4) | | 177 (94.7) | 655(96.5) | | 117 (93.6) | 715(96.5) | |
Maternal and infant characteristics
Maternal and infant characteristics of the study participants are described in Table
2. Most of the pregnancies were planned, 738 (85.2%), and 333 (38.4%) were first pregnancies. Almost all (95.7%) of the study participants had engaged with antenatal care (ANC), and most had attended postnatal care service (76.7%). Twenty-six (3.0%) and 128 (14.9%) were low birth weights and preterm births, respectively. Seventy-one (8.2%) infants were underweight, 529 (61.4%) mothers initiated early breastfeeding, and 577 (66.6%) strongly agreed that their infants were satisfied with breastfeeding. The incidence (95% CI) of diarrhea, ARI, and malnutrition were 17.0% (14.5–19.6), 21.6% (18.89–24.49), and 14.4% (12.2–16.9) respectively. During the follow up period, the episodes of ARI and diarrhea ranged from 1 to 5 and 1 to 4 respectively.
Table 2
Characteristics of maternal and infant participants to those with and without Diarrhea, Acute Respiratory Infection (ARI), and Malnutrition in Gondar Town, Ethiopia, (n = 866)
Pregnancy intention | | | 0.562 | | | 0.397 | | | 0.688 |
Planned | 123 (83.7) | 615(85.5) | | 163 (87.2) | 575(84.7) | | 108 (86.4) | 630(85.0) | |
Unplanned | 24 (16.3) | 104(14.5) | | 24 (12.8) | 104(15.3) | | 17 (13.6) | 111(15.0) | |
Parity of the mother | | | 0.793 | | | 0.675 | | | 0.432 |
1 | 53 (36.0) | 280(38.9) | | 77 (41.2) | | | 43 (34.4) | 290(39.1) | |
2 | 47 (32.0) | 224(31.2) | | 55 (29.4) | | | 45 (36.0) | 226(30.5) | |
3–8 | 47 (32.0) | 215(29.9) | | 55 (29.4) | | | 37 (29.6) | 225(30.4) | |
Antenatal care service uptake (at least one) | 0.142 | | | 0.014 | | | 0.871 |
Yes | 144 (98.0) | 685(95.3) | | 185 (98.9) | 644(94.8) | | 120 (96.0) | 709(95.7) | |
No | 3 (2.0) | 34(4.7) | | 2 (1.1) | 35(5.2) | | 5 (4.0) | 32(4.3) | |
Postnatal care service | | | 0.562 | | | 0.016 | | | 0.000 |
Yes | 110 (74.8) | 554(77.0) | | 131 (70.1) | 533(78.5) | | 76 (60.8) | 588(79.3) | |
No | 37 (25.2) | 165(23.0) | | 56 (29.9) | 146(21.5) | | 49 (39.2) | 153(20.6) | |
Low birth weight | | | 0.016 | | | 0.000 | | | 0.452 |
Yes | 9 (6.1) | 20(2.4) | | 14 (7.0) | 15(1.9) | | 5 (4.1) | 22(2.8) | |
No | 138 (93.9) | 699(97.6) | | 173 (93.0) | 664(98.1) | | 120 (95.9) | 719(97.2) | |
Preterm birth | | | 0.770 | | | 0.311 | | | 0.432 |
Yes | 23 (15.7) | 108(14.7) | | 33 (17.2) | 97(14.2) | | 21 (17.2) | 107(14.5) | |
No | 124 (84.3) | 611(85.3) | | 154 (82.8) | 582(85.8) | | 104 (82.8) | 634(85.5) | |
Exposure to coffee in pregnancy | 0.429 | | | 0.065 | | | 0.075 |
Daily | 64 (43.5) | 293(40.7) | | 89 (47.6) | 268(39.5) | | 58 (46.4) | 299(40.4) | |
Sometimes | 44 (30.0) | 255(35.5) | | 52 (27.8) | 247(36.4) | | 32 (25.6) | 267(36.0) | |
Never | 39 (26.5) | 171(23.8) | | 46 (24.6) | 164(24.1) | | 35 (28.0) | 175(23.6) | |
Exposure to cigarette in pregnancy | 0.906 | | | 0.331 | | | 0.528 |
Yes | 12(8.2) | 78(10.8) | | 19(10.2) | 71(10.5) | | 11(8.8) | 79(10.7) | |
No | 135(91.8) | 641(89.2) | | 168(89.8) | 608(89.5) | | 114(91.2) | 662(89.3) | |
Nutritional status of the mother | | 0.193 | | | 0.109 | | | 0.186 |
Normal | 131 (89.1) | 664(92.3) | | 177 (94.6) | 618(91.0) | | 111 (88.8) | 684(92.3) | |
Underweight | 16 (10.9) | 55(7.6) | | 10 (5.4) | 61(9.0) | | 14 (11.2) | 57(7.7) | |
Early initiation of breast feeding | | 0.214 | | | 0.000 | | | 0.000 |
Yes | 97 (66.0) | 435(60.5) | | 152 (81.7) | 380(55.8) | | 112 (89.3) | 422(56.8) | |
No | 50 (34.0) | 284(39.5) | | 35 (18.3) | 299(44.2) | | 13 (10.7) | 319(43.2) | |
Care given for infant by | | | 0.004 | | | 0.986 | | | 0.023 |
Mothers | 136 (92.5) | 701(97.5) | | 182 (97.3) | 655(96.5) | | 125 (100.0) | 712(96.1) | |
Housekeeper | 11 (7.5) | 18(2.5) | | 5 (2.7) | 24(3.5) | | 0 (0.0) | 29(3.9) | |
Maternal perception of infant response to breast feeding | 0.110 | | | 0.279 | | | 0.000 |
Strongly agree | 87 (59.2) | 490(68.1) | | 132 (70.6) | 445(65.5) | | 74 (59.2) | 503(67.9) | |
Agree | 56 (38.1) | 214(29.8) | | 53 (28.3) | 217(32.0) | | 42 (33.6) | 228(30.8) | |
Not satisfied | 4 (2.7) | 15(2.1) | | 2 (1.1) | 17(2.5) | | 9 (7.2) | 10(1.3) | |
Univariate associations were observed between diarrhea and LBW (p = 0.016) and infant care (p = 0.004). Univariate associations were also observed between ARI and ANC (p = 0.014), postnatal care (p = 0.016), LBW (p < 0.001), and early initiation of breastfeeding (p < 001). Early initiation of breast feeding (p < 0.001), postnatal care (p < 0.001), breastfeeding satisfaction (p < 0.001), and infant care (p = 0.024) were univariately associated with the risk of malnutrition.
Psycho-social characteristics
The psycho-social characteristics of the study participants are described in Table
3. Fifty-six (6.5%) and 74 (8.5%) of the mothers had antenatal and postnatal depression respectively. In univariate analysis, neither antenatal or postnatal depression were associated with diarrhea, ARI or malnutrition (
p > 0.1 for each). More than half of the study participants, 564 (66.6%), had a good relationship with their partners and 691 (79.8%) had good social support. About 403 (46.5%) women had frequent support from their partner and 547 (63.2%) had poor stress coping abilities. Diarrhea (
p = 0.042) and ARI (
p < 0.001) were associated with stress coping ability.
Table 3
Psycho-social characteristics of participants to those with and without Diarrhea, Acute Respiratory Infection (ARI), and Malnutrition in Gondar Town, Ethiopia, (n = 866)
Marital relationship | | | 0.776 | | | 0.052 | | | 0.946 |
Very good | 35 (26.4) | 167(24.3) | | 48 (25.5) | 158(24.4) | | 29 (25.6) | 176(24.5) | |
Good | 93 (66.0) | 466(66.6) | | 122 (70.1) | 432(65.5) | | 77 (66.1) | 477(66.6) | |
Poor | 10 (7.6) | 61(9.1) | | 8 (4.4) | 64(10.1) | | 9 (8.3) | 64(8.9) | |
Social support | | | 0.05 | | | 0.436 | | | 0.205 |
Good | 126 (85.7) | 565(78.6) | | 153 (81.8) | 538(79.2) | | 105 (84.0) | 586(79.1) | |
Poor | 21 (14.3) | 154(21.4) | | 34 (18.2) | 141(20.8) | | 20 (16.0) | 155(20.9) | |
Partner support | | | 0.251 | | | 0.266 | | | 0.078 |
Always | 74 (52.4) | 318(45.3) | | 93 (49.7) | 302(45.6) | | 60 (50.4) | 332(45.9) | |
Most of the time | 37 (27.2) | 201(29.1) | | 51 (27.3) | 190(29.2) | | 34 (29.6) | 204(28.6) | |
Some of the time | 18 (13.6) | 136(19.7) | | 37 (19.8) | 120(18.4) | | 12 (11.2) | 140(20.0) | |
Rarely | 8 (6.8) | 40(5.8) | | 6(3.2) | 41(6.8) | | 11(8.8) | 39(5.5) | |
Stress coping ability | | | 0.042 | | | 0.000 | | | 0.554 |
Good | 65 (44.2) | 254(35.3) | | 91 (48.7) | 228(33.6) | | 49 (39.2) | 270(36.4) | |
Poor | 82 (55.8) | 465(64.7) | | 96 (51.3) | 451(66.4) | | 76 (60.8) | 471(63.6) | |
Antenatal depression | | | 0.197 | | | 0.714 | | | 0.225 |
Yes | 6(4.1) | 50(6.9) | | 11(5.9) | 45(6.6) | | 5(4.0) | 51(6.9) | |
No | 141(95.9) | 669(93.1) | | 176(94.1) | 634(93.4) | | 120(96.0) | 690(93.1) | |
Postnatal depression | | | 0.140 | | | 0.559 | | | 0.135 |
Yes | 8(5.4) | 66(9.2) | | 14(7.5) | 60(8.8) | | 15(12.0) | 59(8.0) | |
No | 139(94.6) | 653(90.8) | | 173(92.5) | 619(91.2) | | 110(88.0) | 682(92.0) | |
Causal association between depression and infant diarrhea, ARI, and malnutrition
Table
4 shows the results from the TMLE analysis. In the fully adjusted models, there was no association between antenatal depression and the risk of diarrhea, ARI or malnutrition. Specifically, compared to those without antenatal depression, the risk difference for antenatal depression and diarrhea was 0.8% (95%CI: − 9.2, 10.9), − 1.3% (95%CI: − 21.0, 18.5) for ARI, and − 7.3% (95%CI: − 22.0, 21.8) for malnutrition. Similarly, postnatal depression was not associated with diarrhea (risk difference = − 2.4%; 95%CI: − 9.6, 4.9), ARI (risk difference = − 3.2%; 95%CI: − 12.4, 5.9) or malnutrition (risk difference = 0.9%; 95%CI: − 7.6, 9.5). In comparison to the TMLE models, the point estimates for the IRR’s for each of the GEE models were generally much further from the null association i.e. an incidence rate ratio equal to one, although none reached statistical significance (Table
4).
Table 4
Estimates from TMLE showing the association of antenatal and postnatal depression with risk of Diarrhea, ARI, and Malnutrition in Gondar Town (N = 866), Ethiopia, 2018
Diarrhea |
Antenatal depression |
No | 1.00 | 1.00 | | |
Yes | 0.65(0.29,1.45) | 0.57(0.24,1.31) | 0.185 | 0.8% (−9.2, 10.9) |
Postnatal depression |
No | 1.00 | 1.00 | | |
Yes | 0.85(0.46,1.60) | 0.92(0.45,1.78) | 0.811 | -2.4% (−9.6, 4.9) |
Adjusted for history of CMD, low birth weight, husband support, social support, stress coping ability, pregnancy condition, food access of the family, and maternal health care services. |
Acute Respiratory Infection |
Antenatal depression |
No | 1.00 | 1.00 | | |
Yes | 0.85 (0.45,1.60) | 0.92 (0.47,1.78) | 0.798 | −1.3% (−21.0, 18.5) |
Postnatal depression |
No | 1.00 | 1.00 | | |
Yes | 1.10(0.66,1.81) | 1.00(0.58,1.72) | 0.994 | −3.2% (−12.4, 5.9) |
Adjusted for age of the mother, age of the infant, maternal service uptake, fear to give birth, marital situation, husband support, social support, pregnancy need, food access, and occupation. |
Malnutrition |
Antenatal depression |
No | 1.00 | 1.00 | | |
Yes | 0.47(0.16,1.40) | 0.61(0.19,1.97) | 0.407 | −7.3% (−22.0, 21.8) |
Postnatal depression |
No | 1.00 | 1.00 | | |
Yes | 1.48(0.83,2.64) | 1.43(0.71,2.89) | 0.314 | 0.9% (−7.6, 9.5) |
Adjusted for maternal services, parity, income, food access, occupation, educational status, marital situation, marital status, partner support, social support, history of common mental disorder, pregnancy condition, and nutritional status of the mother. |
In the mediation analysis using GSEM, results showed that: (i) There was no indirect effect of antenatal depression via postnatal depression on the risk of either diarrhea (p = 0.213), ARI (p = 0.660) or malnutrition (p = 0.182); (ii) There was no indirect effect of antenatal depression on the risk of malnutrition via LBW (p = 0.551) or early initiation of breastfeeding (p = 0.705). There were also no significant interactions between antenatal and postnatal depression with social support, partner support, and stress coping ability on the risk of diarrhea, ARI, and malnutrition (p > 0.2 for each). In the sensitivity analysis of the TMLE models, including the potential mediators did not change any of the substantive conclusions.
Discussion
This study evaluated the incidence of diarrhea, acute respiratory infection (ARI), and malnutrition among infants age to 6 months in Gondar, Ethiopia and whether a causal relationship exists between perinatal depression and each of these outcomes. The incidence of diarrhea, ARI, and malnutrition was 17.0, 21.6, and 14.4%, respectively. Neither antenatal or postnatal depression appeared to be causally associated with the risk of diarrhea, ARI, and malnutrition.
The estimated incidence of diarrhea and ARI was slightly lower than that estimated in predominantly rural areas in Ethiopia, where there was a diarrhea and ARI incidence of 26.0 and 25% respectively [
24]. These differences may be due to the method of measurement, the age of the included infants and the study setting. Diarrhea and ARI incidence are higher in rural areas compared to urban areas and increase with infant age [
65]. Similarly, the incidence of malnutrition in the current study was lower than the 21.5% reported in a population-based cohort study conducted in other rural areas [
22]. This could be due to differences in the screening tool used for malnutrition. In the current study, a MUAC of less than 110 mm was used as a cut of value [
41,
42], indicating a sufficiently severe stage of malnutrition to put infants at considerable risk of death. Despite a substantial reduction of diarrhea, ARI, and malnutrition in Ethiopia in the last 15 years [
66], the estimates from the current and previous studies demonstrate that these morbidities continue to be a significant public health problem in Ethiopia.
The main finding in this study was that antenatal depression was not causally associated with the risk of diarrhea, ARI, or malnutrition. This finding differs from previous Ethiopian community based cross-sectional [
23] and cohort [
24] studies which have reported significant associations between maternal common mental disorders (CMDs) and the risk of diarrhea and upper respiratory infection [
20] but not ARI [
21]. Elsewhere, a UK population based cohort study of children under the age of 4 years observed a 27% higher risk of episodes of lower respiratory tract infection amongst mothers that had experienced perinatal depression [
67]. Similarly, antenatal depression predicted a higher risk of respiratory tract infections in offspring aged up to 10 months in Finland [
68]. However, a meta-analysis of two prospective cohort studies demonstrated no association between antenatal depression and the risk of diarrhea [
69]. Wasting, underweight, and stunting were also not associated with antenatal depression in Ethiopia in separate cross-sectional and cohort studies [
22,
23].
Consistent with the above findings, this study found no causal association between postnatal depression and the risk of malnutrition, ARI, and diarrhea. Similarly, there was no association between CMDs during the postnatal period and underweight or stunting in Peru, Vietnam, India, and Ethiopia [
70] and in two other community-based studies in Ethiopia [
22,
23]. However, other studies in African countries have shown significant associations [
10,
71‐
73]. Regarding risk of ARI and diarrhea, similar findings to our own were reported in community based cross-sectional [
23] and cohort [
24] studies in Ethiopia. However, postnatal depression did increase the risk of illness in infants aged four to 12 weeks and children under-5 years in prospective cohort studies conducted in Ghana [
74] and Bangladesh [
75] respectively. Further, a systematic review and meta-analysis reported postnatal depression increased the risk factor for diarrhea [
69] and malnutrition [
76], however, these reviews had an issue of heterogeneity in depression measurement. Thus, while the current and other studies in Ethiopia discount postnatal depression as a risk factor for diarrhea and ARI, studies in other African countries have observed associations. In the current study, unmeasured confounders such a sanitation, immunization, and lack of safe water had the potential to bias the estimates in either direction [
66,
77]. However, the use of a doubly robust method will have helped reduce the risk of bias in comparison to previous studies that used standard regression techniques.
Despite a lack of clear evidence, various mechanisms have been suggested to explain an association between common mental disorders during the perinatal period and the risk of infant morbidity. For instance, common mental disorders during pregnancy can affect hypothalamic-pituitary-adrenocortical function, thereby influencing the development of the immune system in the offspring and subsequently increasing susceptibility to infections [
78‐
80]. CMD might also negatively or positively affect the health-seeking behavior and lifestyle of the parents [
81,
82]. However, we observed no evidence for a mediating effect for either low birth weight, early initiation of breastfeeding, or postnatal depression on any of the three outcomes. The lack of mediating effects was unsurprising given the lack of any overall association.
Strength and limitations
This is the first prospective cohort study, conducted in an urban setting of Ethiopia, investigating the causal effect of antenatal and postnatal depression (measured using the EPDS) on the risk of diarrhea, ARI and malnutrition among infants aged under 6 months. We used Targeted Maximum Likelihood Estimation (TMLE) to assess the causal effects. Whilst there were several potential unobserved confounders such as personal hygiene, water access, latrine availability and cleanliness, various forms of violence, and immunization status, the method we used is doubly robust, such that model misspecification for either the exposure or outcome due to unobserved confounding reduces the potential for bias [
58,
59].
The results of this study need to be considered under the assumptions for valid causal inference. This includes the positivity assumption, which states that all individuals have a positive probability of exposure. Since women with a high likelihood of having severe depression were excluded, this might have introduced a potential selection bias. In addition, the use of MUAC to assess malnutrition has not been validated in Ethiopia in infants of age under 4 months, and this might have either under or overestimated the true infant nutritional status. Similarly, we employed proxy indicators or symptoms (as established in the IMNCI guideline) to identify infants with diarrhea and ARI, which may have led to either under or over-diagnosis of cases. Nonetheless, the IMNCI guideline is recommended by the World Health Organization for use in primary health facilities and demonstrates high sensitivity and specificity.
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