Postnatal infection surveillance by telephone in Dar es Salaam, Tanzania: An observational cohort study.

INTRODUCTION: Maternal and newborn infections are important causes of mortality but morbidity data from low- and middle-income countries is limited. We used telephone surveillance to estimate infection incidence and risk factors in women and newborns following hospital childbirth in Dar es Salaam.
METHODS: We recruited postnatal women from two tertiary hospitals and conducted telephone interviews 7 and 28 days after delivery. Maternal infection (endometritis, caesarean or perineal wound, or urinary tract infection) and newborn infection (umbilical cord or possible severe bacterial infection) were identified using hospital case-notes at the time of birth and self-reported symptoms. Adjusted Cox regression models were used to assess the association between potential risk-factors and infection.
RESULTS: We recruited 879 women and interviewed 791 (90%). From day 0-7, 6.7% (49/791) women and 6.2% (51/762) newborns developed infection. Using full follow-up data, the infection rate was higher in women with caesarean childbirth versus women with a vaginal delivery (aHR 1.93, 95%CI 1.11-3.36). Only 24% of women received pre-operative antibiotic prophylaxis before caesarean section. Infection was higher in newborns resuscitated at birth versus newborns who were not resuscitated (aHR 4.45, 95%CI 2.10-9.44). At interview, 66% (37/56) of women and 88% (72/82) of newborns with possible infection had sought health-facility care.
CONCLUSIONS: Telephone surveillance identified a substantial risk of postnatal infection, including cases likely to have been missed by hospital-based data-collection alone. Risk of maternal endometritis and newborn possible severe bacterial infection were consistent with other studies. Caesarean section was the most important risk-factor for maternal infection. Improved implementation of pre-operative antibiotic prophylaxis is urgently required to mitigate this risk.

Introduction

Preventing maternal and newborn infections is a high priority in the World Health Organization’s (WHO) vision of good quality care for pregnant women and newborns [1]. Pregnancy-related sepsis is estimated to cause 11% of maternal mortality [2] and infection is responsible for 23% of newborn deaths [3] with the vast majority in low- and middle-income countries (LMICs). Increasing health-facility births in LMICs [4] presents an opportunity to reduce disease incidence through strengthened infection prevention initiatives.

Despite the importance of maternal and newborn infection, we have limited knowledge of the frequency in high-burden countries. A systematic review of maternal peripartum infection included only seven sub-Saharan Africa (SSA) studies (one from Tanzania [5]) and none were considered high quality [6]. From meta-analysis, the regional estimate for endometritis was 1.7% and for wound infection was 3.4%. A systematic review of possible severe bacterial infection (pSBI) using the Young Infant Clinical Signs Study (YICSS) criteria [7] estimated 6.2% of newborns in SSA were affected (six studies, none from Tanzania). The case-fatality risk was 14.1% [8].

The majority of severe maternal infections occur postpartum, arising from the genito-urinary tract or wounds [9, 10], and presenting after the woman has been discharged home following childbirth [11]. The majority of newborn deaths from infection occur after the first week of life [3]. Community follow-up is therefore necessary to capture all cases of infection. Home visits are resource intensive, consequently many studies only report infection up to the time of hospital discharge following facility childbirth. Mobile telephone surveillance is a possible alternative, with emerging evidence of feasibility and validity to monitor surgical site infection (SSI) in SSA [12, 13], and postnatal outcomes in India [14].

Responding to the limited data on maternal newborn infection incidence in SSA our observational cohort study aimed to estimate the incidence and risk factors for infection in women and newborns in the four weeks following hospital childbirth in urban Tanzania, using hospital case-notes from the time of birth and telephone surveillance. We also assessed the feasibility of mobile telephone assessment for infection, described care-seeking behaviour following infection and explored possible consequences of infection; hospital readmission, depression and reduced maternal function.

Methods

This study was a collaboration between London School of Hygiene and Tropical Medicine (LSHTM) and Ifakara Health Institute (IHI) and based at two of the three public Regional Referral Hospitals in Dar es Salaam; Amana (Ilala district) and Temeke (Temeke district). Each hospital conducts approximately 1,000 births per month. It was a sub-study of a pilot evaluation of training in environmental cleaning [15].

Two research nurses per hospital recruited eligible women from postnatal wards every Monday to Thursday. They sampled from all women who gave birth in the previous 24 hours using a random number application [16] with probability proportional to delivery mode (caesarean or vaginal). Eligible women were aged 18 years or older with access to at least one mobile telephone and providing signed or witnessed thumbprint consent. Women admitted to the intensive care unit were ineligible. Women provided up to three mobile telephone numbers; one or two of their own and one for a relative or neighbour. Replacements were sampled in the same way when potential participants were unavailable or ineligible.

Two research nurses at IHI offices in Dar es Salaam interviewed each woman twice by telephone in Kiswahili, starting seven and 28 days after recruitment. Nurses made four telephone call attempts, over seven days, to reach each woman.

Outcomes and exposures

The primary outcomes were 1) possible maternal postnatal infection (one or more of caesarean surgical site infection, urinary tract infection, perineal wound infection or endometritis) and 2) possible newborn infection (either of pSBI or umbilical cord infection). Each outcome was measured as a rate, and as the day 7 (early infection) and day 8–28 cumulative risk. Infections were identified from women’s hospital case-notes around the time of childbirth or from self-reported symptoms during telephone interview using standard definitions [7, 17, 18]. These definitions were adapted by the first author to include only symptoms and signs easily reported by the women (Table 1). Secondary outcomes were each individual infection listed above, plus mastitis.

Table 1

Syndromic infection definitions used.

Infection	Questions to women	Definition	Standard definition adapted
Caesarean Section Surgical Site Infection (SSI)	At the site of your caesarean section (cut/operation on your abdomen) have you experienced:	Either I. OR, (V. AND one or more of II-IV.), OR two or more of VI-VIII	CDCa
	I. Pus discharge
	II. Pain
	III. Swelling
	IV. Redness
	V. Wound breakdown (wound edges separated)
	Have you experienced:
	VI. Fever
	VII. Abdominal pain
	VIII. Foul-smelling or pus vaginal discharge
Urinary Tract Infection (UTI)	Have you experienced:	Either (I. and II.) OR, three or more of I-V.	SIGNb
	I. Pain passing urine
	II. Urinary frequency–passing urine more often
	III. Urinary urgency–need to pass urine quickly/difficulty in holding urine
	IV. Fever
	V. Abdominal pain
Perineal wound infection	At the site of a perineal wound (cut or tear in the vagina) have you experienced:	Either, I. OR, (IV AND one or both of II and III.)	CDCa
	I. Pus discharge
	II. Pain
	III. Swelling
	IV. Wound breakdown (wound edges separated)
Endometritis	Have you experienced:	Two or more of I-III where II is not explained by UTI and III is not explained by perineal wound infection.	CDCa
	I. Fever
	II. Abdominal pain
	III. Foul-smelling or pus vaginal discharge
		In women with caesarean section this was counted as an organ space SSI
Mastitis	Have you experienced:	Either, I. OR, both II. and III.	CDCa
	I. Swollen, hard area of the breast
	II. Painful, red breast
	III. Fever
pSBI	Has your baby experienced:	One or more of I-VII.	YICSSc
	I. Fever
	II. Very cold (low temperature)
	III. Very fast breathing
	IV. Chest indrawing (sucking in the ribs when breathing)
	V. Convulsions/fits
	VI. Poor feeding/not feeding
	VII. Only moving when stimulated
Umbilical cord infection	Has your baby experienced:	One or both of I. and II.	CDCa
	I. Redness around the umbilical cord stump
	II. Pus discharge from umbilical cord stump

a)Centres for Disease Control [18]

b) Scottish Intercollegiate Guidelines Network [17]

c)Young Infants Clinical Signs Study [7].

Potential risk factors were extracted from hospital case-notes; maternal age, gestational age, parity, HIV, diabetes, hypertensive disorder, haemorrhage, prelabour rupture of membranes (PROM), induction of labour, delivery mode, postpartum haemorrhage (PPH) and infection during labour. Possible consequences of infection collected during telephone interview were self-reported readmission, depression assessed using a validated 5-question modified Edinburgh Postnatal Depression Scale (EPDS) and functionality according to five common postpartum activities (S1 Appendix).

Data collection

Data was entered on tablets with Open Data Kit (ODK), using unique identification (ID) numbers to maintain confidentiality. Data was extracted from maternal paper case-notes after hospital discharge, including demographics, pregnancy and childbirth history, infection diagnosed during admission and antibiotics prescribed (S2 Appendix). Telephone interviews with women consisted of pre-coded closed questions on the history of specific symptoms of infection, day of symptom onset, care-seeking behaviour, and readmission to hospital. At day-28, women were also asked questions on depression and function (S1 Appendix). Women with infection symptoms were advised to attend a health-facility if they hadn’t already. In cases of maternal depression or neonatal death, women were offered referral to social welfare liaison for counselling and support.

Research nurses received six days training in recruitment and data collection, including two days at the hospitals when they piloted the tools on 24 women. Telephone interview nurses additionally conducted pilot interviews with the same 24 women over two days.

Study size

With 900 women and an estimated 10% loss to follow-up at day-28, we would have 95% confidence to estimate a maternal infection risk of 3%±1.2% with 80% power. Our daily recruitment target was 12–20 women per hospital.

Data management

Data was cleaned and analysed using STATA 16. Gestational age was grouped as preterm (<37 weeks) or term (37–42 weeks). The depression score was grouped as no depression (0–5) or possible depression (6–30). Maternal function questions were analysed individually as “any” or “no difficulty” in performing the function.

Duplicate ID numbers and data entry errors were corrected where possible using hospital case-notes or comparing with other study data. Any remaining discordant data was dropped. There was inconsistency in the occurrence of stillbirths between data sources, therefore stillbirths were not analysed. Data on twin and triplet newborns was also inconsistent and in addition an error in ODK programming meant only data from the first baby was useable.

Statistical analysis

Women’s demographic and pregnancy data was described by delivery mode. Rates of infection were calculated from delivery until the day-28 telephone call using reported days from delivery to start of symptoms. Symptoms reported at both day-7 and day-28 were counted as distinct infection events if they started over 14 days apart, or if they met criteria for different infection types and started over seven days apart, or if initial symptoms had resolved by the day-7 interview. Date of death and infection data were not collected from babies who died before the day-7 interview, therefore these babies were excluded from infection outcome analyses. Babies who died after the day-7 interview contributed to infection analyses up to day 7. Using Cox regression with robust standard errors to account for clustering by person, we explored associations between potential risk factors and the rate of maternal postnatal infection or possible newborn infection. Proportional hazards assumptions were checked using tests based on Schoenfeld Residuals. Factors showing evidence of association in the crude analysis (p<0.1) were explored further in multivariable models. Maternal age and delivery hospital were considered a priori confounders for risk of maternal postnatal infection. We restricted the parameters in the final models to 10% of the number of outcomes. For missing risk-factor data, we carried out multiple imputation using chained equations (MICE) because most variables were categorical, creating 10 imputed datasets. Delivery mode and hospital were included as auxiliary variables. Women whose case-notes were missing were excluded from risk-factor analysis.

We report the highest level of care sought by women and newborns with possible infection and the percentage readmission to hospital for those with and without infection. We describe maternal depression and function at day-28 and explore associations with early postnatal infection using chi-squared tests and logistic regression.

Ethics

The study was approved by the Tanzanian National Institute for Medical Research, IHI Institutional Research Board and LSHTM Research Ethics Committee. Written informed consent was obtained from women on the postnatal wards. Willingness to continue in the study was confirmed at the start of each telephone interview. There was no public or patient involvement in the study design or interpretation of results. The Soapbox Collaborative supported the study following external peer review of the study proposal.

Results

Between 15th March and 9th May 2018, research nurses recruited 879 women into the study, sampling from a total of 2,110 deliveries (18% caesarean section) (Fig 1). We interviewed 791 (90%) women at least once, providing data until day 7, and 753 (86%) completed the day-28 interview. Final interview occurred between 7 and 43 (median 29) days after delivery. Most women whose only interview was at day-28, reported that their telephone battery was not charged at day-7.

Fig 1

Flow diagram.

Case-notes were not located for 39 women. In the remaining 840, missing data was minimal except gestational age (39%). Mean age was 25 (range 18–45) years. Fewer than 3% of women were referred-in. Induction and augmentation of labour, including artificial rupture of membranes, were uncommon (each <3%) but occurred more frequently at Amana Hospital than Temeke Hospital (S2 Table). Among vaginal births (n = 692), seven were breech and three were by vacuum extraction. Vaginal tears were experienced after 36% of vaginal deliveries and episiotomy was rare (Table 2). Among 829 liveborn babies, bag-and-mask resuscitation and admission were more common both following caesarean section and at Amana Hospital (Table 2, S1 Table). Average length of stay after delivery was 0.8 days following vaginal delivery (range 0–8) and 2.4 days post-caesarean section (range 0–7).

Table 2

Demographic, pregnancy and newborn factors by mode of delivery for 840 women and 829 liveborn babies with maternal hospital case-notes.

	Vaginal Delivery n(%) (N = 692)	Caesarean Section n(%) (N = 148)	Total
			n(%) (N = 840)
Maternal age in years
18–24	288 (41.6)	50 (33.8)	338 (40.2)
25–29	193 (27.9)	42 (28.4)	235 (28.0)
30+	197 (28.5)	52 (36.1)	249 (29.6)
Missing	14 (2.0)	4 (2.7)	18 (2.1)
Parity
Nulliparous	234 (33.8)	52 (35.1)	286 (34.1)
1	205 (29.6)	50 (33.8)	255 (30.4)
2	125 (18.1)	23 (15.5)	148 (17.6)
3+	106 (15.3)	19 (12.8)	125 (14.9)
Missing	22 (3.2)	4 (2.7)	26 (3.1)
Preterm birth (<37 weeks gestation)	59 (8.5)	22 (14.9)	81 (9.6)
Missing	287 (41.5)	42 (28.4)	329 (39.2)
Hypertensive disordersa	18 (2.6)	16 (10.8)	34 (4.1)
Missing	4 (0.6)	2 (1.4)	6 (0.7)
HIV	29 (4.2)	8 (5.4)	37 (4.4)
Missing/not available	14 (2.0)	1 (0.7)	15 (1.8)
PROM	25 (3.6)	4 (2.7)	29 (3.5)
Missing	2 (0.3)	1 (0.7)	3 (0.4)
Episiotomy	10 (1.5)	NA	10 (1.2)
Missing	14 (2.0)	NA	14 (1.7)
Perineal tear	250 (36.1)	NA	250 (29.8)
Missing	3 (0.4)	NA	3 (0.4)
PPH	7 (1.0)	2 (1.4)	9 (1.1)
Missing	2 (0.3)	0	2 (0.2)
Antibiotics in labour	26 (3.8)	36 (24.3)	62 (7.4)
Missing	5 (0.7)	1 (0.7)	6 (0.7)
Antibiotics postpartum	382 (55.2)	139 (93.9)	521 (62.0)
Missing	5 (0.7)	3 (2.0)	8 (1.0)
Newborn Factors	Vaginal (N = 681)	CS (N = 148)	Total (N = 829)
Apgar Score at 5 minutes <7	5 (0.7)	5 (3.4)	10 (1.2)
Missing	2 (0.3)	1. (0.7)	3 (0.4)
Bag and mask resuscitation	9 (1.3)	8 (5.4)	17 (2.1)
Missing	2 (0.3)	2 (1.4)	4 (0.5)
Admission	10 (1.5)	12 (8.1)	22 (2.7)
Missing	0	2 (1.4)	2 (0.2)

aHypertensive disorders: 2 eclampsia, 19 pre-eclampsia, 17 pregnancy-induced hypertension.

Antenatally, 7.4% of women received antibiotics, primarily for prophylaxis before caesarean section or following PROM. Postnatally, 62% of all women were prescribed antibiotics: 94% of women undergoing caesarean section and 98% of all women giving birth at Amana hospital were prescribed antibiotics (Table 3).

Table 3

Reason for antibiotics prescribed to women in hospital during labour and postpartum by delivery mode.

	Vaginal Delivery n (%)	Caesarean Section n (%)	Total
Antibiotics in labour	N = 26	N = 36	N = 62
Caesarean section prophylaxis	0	34 (94.4)	34 (54.8)
PROM	14 (53.9)	2 (5.6)	16 (25.8)
UTI	1 (3.9)	0	1 (1.6)
Other	8 (30.8)	0	8 (12.9)
None	3 (11.5)	0	3 (4.8)
Antibiotics postpartum	N = 382	N = 139	N = 521
Caesarean section prophylaxis	0	131 (94.2)	131 (25.1)
PROM	2 (0.5)	0	2 (0.4)
Perineal suture	172 (45.0)	0	172 (33.1)
UTI	1 (0.3)	0	1 (0.2)
Routine	190 (49.7)	0	190 (36.5)
IUD	4 (1.1)	0	4 (0.8)
Unknown/not recorded	13 (3.4)	8 (5.8)	21 (4.0)

Infection risk and rate

No postnatal maternal infections were documented in hospital case-notes at the time of birth and there were no maternal deaths. Among all 791 women with at least one telephone interview, 47 (5.9%) reported possible postnatal infection starting day 0–7. Symptoms of UTI affected 22 (2.8%) women and symptoms of endometritis affected 12 (1.5%). Among 146 women with caesarean section, 15 (10.3%) reported possible postnatal infection of whom 12 (8.2%) had symptoms of SSI (Table 4). From day 8–28, 9/753 (1.2%) developed possible postnatal infection. The rate of possible infection was 79.4 (95% Confidence Interval (CI) 61.1–103.2) per 1000 women per month.

Table 4

Maternal and newborn infections occurring up to 7 days after delivery.

Maternal infection	Vaginal delivery n(%) N = 645	Caesarean section n(%) N = 146	Total n(%) N = 791
Postnatal infection	32 (5.0)	15 (10.3)	47 (5.9)
Endometritis	12 (1.9)	NA	12 (1.5)
SSI	NA	12 (8.2)	12 (1.5)
Perineal wound infection	7 (1.1)	0	7 (0.9)
UTI	15 (2.3)	7 (4.8)	22 (2.8)
Mastitis	13 (2.0)	3 (2.1)	16 (2.0)
Newborn infection	N = 621	N = 141	N = 762
Possible newborn infection	40 (6.4)	11 (7.8)	51 (6.7)
pSBI	36 (5.8)	11 (7.8)	47 (6.2)
Umbilical cord infection	5 (0.8)	0	5 (0.7)

Before the first interview, 28 (3.5%) babies were stillborn or died and one was missing infection data. Of the remaining 762 babies, 51 (6.7%) developed possible newborn infection from day 0–7, almost entirely attributable to pSBI (47, 6.2%) (Table 4). From day 8–28, another six babies died and 30/719 (4.3%) babies developed possible infection, one of whom had two episodes of infection. The rate of possible infection was 121.1 (95% CI 97.5–150.3) per 1000 babies per month. Three of these babies were diagnosed with sepsis in the maternal case-notes. For two of these three cases, no infection symptoms were reported by the mother at telephone interview.

Women sought care in a health facility following 37/56 (66%) episodes of possible postnatal infection: 24 (43%) at their delivery hospital, 8 (14%) at another hospital, and 5 (9%) at a lower level health facility. Babies were taken to a health facility following 72/82 (88%) episodes of possible infection: 38 (46%) to the delivery hospital, 25 (30%) to another hospital, and 9 (11%) to a lower level health facility.

Associations with infection

There was evidence that caesarean delivery doubled the rate of possible maternal postnatal infection compared to women who had a vaginal delivery, and this association remained after adjusting for maternal age and hospital (adjusted Hazard Ratio (aHR) 1.93, 95% CI 1.11–3.36, p = 0.02). There was also weak evidence of an association between women’s age-group and infection (p = 0.06) with the highest infection rates occurring in women aged 25–29 (Table 5).

Table 5

Association between potential risk-factors and rate of possible maternal postnatal infection.

Factor	Total women	Episodes of postnatal infection	Person-time (months)	Rate of infection per 1000 person months	Crude HR (95% CI)	Wald p-value	Adjusted HR (95% CI)	Wald p-value
					N = 754a		N = 754 a
All women	791	56	705.3	79.4 (61.1–103.2)
Delivery mode
Vaginal	645	39	578.1	67.5	1	0.02	1	0.02
Caesarean section	146	17	127.3	133.6	1.95 (1.12–3.37)		1.93 (1.11–3.36)
Maternal age (years)
18–24	303	15	167.9	56.0	1	0.05	1	0.06
25–29	212	23	186.0	123.6	2.20 (1.15–4.28)		2.14 (1.12–4.09)
30+	223	16	204.3	78.3	1.43 (0.72–2.84)		1.37 (0.69–2.70)
Hospital
Amana	403	28	362.0	77.4	1	0.87	1	0.98
Temeke	388	28	343.4	81.5	1.04 (0.62–1.75)		1.01 (0.60–1.70)
Parity
0	252	15	224.8	66.7	1	0.81
1	233	19	206.9	91.8	1.33 (0.69–2.56)
2	131	11	115.0	95.7	1.37 (0.65–2.89)
3+	113	8	103.6	77.2	1.16 (0.48–2.81)
Preterm birth (<37 weeks)
No	392	30	346.5	86.6	1	0.89
Yes	69	5	62.5	80.1	0.94 (0.37–2.35)
Antibiotics in labour
No	697	48	622.6	77.1	1	0.17
Yes	51	6	43.7	137.3	1.75 (0.78–3.91)
Postpartum antibiotics
No	277	18	246.4	73.0	1	0.49
Yes	469	37	417.9	88.5	1.22 (0.69–2.16)

aValues imputed for variables with missing data, except for Preterm birth where the amount of missing data was considered too large to impute.

Results shown if >2 infections in a single category. Full results in S2 Table.

Bag-and-mask resuscitation at birth was strongly associated with possible newborn infection compared to babies who were not resuscitated (aHR 4.45, 95% CI 2.10–9.44, p<0.001), however this was a rare exposure (n = 11 babies). There was weak evidence for increased possible newborn infection if the mother received antibiotics in labour compared to mothers who did not (Table 6).

Table 6

Association between potential risk factors and rate of possible newborn infection.

Factor	Total newborns	Episodes of possible infection	Person-time (months)	Rate of infection per 1000 person months	Crude HR (95% CI)	Wald p-value	Adjusted HR (95% CI)	Wald p-value
					N = 725a		N = 725 a
All babies	762	82	677.4	121.1 (97.5–150.3)
Resuscitation (bag and mask)
No	709	75	629.9	119.1	1	<0.001	1	<0.001
Yes	11	5	8.7	574.3	4.61 (2.35–9.04)		4.45 (2.10–9.44)
Antibiotics in labour
No	674	69	598.5	115.3	1	0.01	1	0.08
Yes	47	10	39.9	250.9	2.15 (1.18–3.91)		2.00 (0.93–4.30)
Delivery mode
Vaginal	621	64	552.2	115.9	1	0.35	1	0.95
Caesarean section	141	18	125.1	143.8	1.24 (0.74–2.09)		1.02 (0.55–1.91)
PROM
No	698	75	617.7	121.4	1	0.37	1	0.76
Yes	24	4	22.1	180.6	1.53 (0.61–3.84)		1.16 (0.45–2.99)
Maternal age (years)
18–24	291	29	256.9	112.9	1	0.51
25–29	203	27	280.4	149.6	1.34 (0.79–2.28)
30+	216	22	193.0	114.0	1.05 (0.60–1.84)
Hospital
Amana	388	41	347.1	118.1	1	0.94
Temeke	374	41	330.3	124.1	1.04 (0.67–1.61)
Preterm (<37 weeks gestation)
No	376	38	330.6	114.9	1	0.65
Yes	67	8	59.5	134.5	1.18 (0.57–2.44)
Postpartum antibiotics
No	266	21	236.8	88.7	1	0.07
Yes	452	58	399.5	145.2	1.59 (0.96–2.62)

aValues imputed for variables with missing data, except for Preterm birth where the amount of missing data was considered too large to impute.

Results not shown if <3 infections in a single category. Full results in S3 Table.

In the first seven days postnatal 7/762 mother-baby pairs both experienced possible infection. Mother’s with postnatal infection in the first 7 days had an increased risk of their baby suffering possible newborn infection during this time period, compared to mother’s without infection (crude Odds Ratio 2.74, 95%CI 1.16–6.48, p = 0.02).

Consequences of infection

At the day-7 interview, 5/43 (12%) women with possible postnatal infection reported they had been readmitted to hospital as compared with only 5/696 (0.7%) women without infection. All women readmitted with infection had given birth by caesarean section. Among 713 babies alive at the day-7 interview, 44% with possible infection had been readmitted to hospital compared with 1.8% of those without.

Depression scores ranged from 0–10/30 among 753 women at day-28 interview and 31 (4%) had possible depression (score > = 6). Among 43 women with early postnatal infection (day 0–7), 4 (9.3%) developed possible depression versus 27 (3.8%) of those without infection (OR 2.1, 95% CI 0.64–6.89, p = 0.22, adjusting for death of the baby).

At day-28 interview, 103/752 (13.7%) women reported difficulty with housework and 8/751 (1.1%) reported difficulty washing themselves. Among women with a living baby, 43/718 (6.0%) reported difficulty carrying or caring for their baby and 99.7% were exclusively breastfeeding. Difficulty with each activity was reported more frequently among women with possible early postnatal infection compared to those without infection, but statistical evidence was inconsistent (Table 7).

Table 7

Associations between early maternal postnatal infection (day 0–7) and maternal function at day 28.

	Difficulty washing	Difficulty with housework	Difficulty carrying baby	Difficulty caring for baby
	n/N (%)	n/N (%)	n/N (%)	n/N (%)
Postnatal infection
No	6/709 (0.9)	94/709 (13.3)	39/679 (5.7)	38/679 (5.6)
Yes	2/42 (4.8)	9/43 (20.9)	4/39 (10.3)	5/39 (12.8)
Chi2 p-value	0.02	0.16	0.25	0.06

Discussion

We conducted telephone interviews with 791 women at seven and/or 28 days after hospital childbirth in Dar es Salaam, Tanzania. We estimated a rate of 79.4 possible maternal and 121.1 possible newborn infections per 1000 person-months. Women with caesarean birth had twice the rate of infection. Newborns resuscitated at birth had over four times the rate of infection. Women and newborns with possible infection had substantially higher readmission rates compared with those without infection, and there was a trend towards increased depression risk following early infection. Telephone surveillance proved feasible: 97% of the initial sample had access to a mobile telephone and 90% of all recruited women were interviewed at least once.

Global incidence of pregnancy-related infection estimated by the Global Burden of Disease study 2017 equates to 8.2% of livebirths [19], and the recent Global Maternal Sepsis Study (GLOSS) reports prevalence of infection in hospitalised pregnant and postpartum women of 70.4 per 1000 livebirths [10]; however, their broader case definitions prevent direct comparison with our study. Our incidence of endometritis at day-7 (1.5%) is consistent with the 1.7% (95% CI 1.4–2.1%) estimate for SSA from a recent meta-analysis [6]. However, we observed a caesarean surgical site infection risk of 8.2%, which is lower than the 15.6% estimate from a systematic review for SSA [20]. Our incidence of pSBI (6.2%) was the same as the estimate for SSA from a meta-analysis of studies in which health or community workers applied YICSS criteria [21].

Caesarean section is an established risk factor for maternal infection and sepsis [9, 10, 22] and in our study carried a higher risk of both SSI and UTI than vaginal birth. Increasing rates of caesarean childbirth and evidence of antimicrobial resistance (AMR) in subsequent infections [23] demand enhanced infection prevention measures. Pre-operative prophylactic antibiotics are effective [24] and recommended in Tanzania [25], but were documented before only 24% of caesarean sections. Newborn infection could result from pathogens introduced during resuscitation, explaining the strong association seen. Additionally, sick newborns requiring ventilation are at increased risk of infection, supporting calls to improve both intrapartum care and postnatal infection prevention [26].

Expected associations between prematurity, PROM, PPH, HIV, and either maternal or newborn infection were not evident, but these factors were reported less frequently than expected. Induction and augmentation of labour were similarly infrequent. This could reflect poor documentation at the hospitals or difficulties in extraction. Postpartum antibiotics were not associated with reduced infection incidence, providing no justification for universal prescribing observed at one study hospital. This practice is not recommended nationally or internationally [27], could be a driver of AMR and needs to be challenged. There was some evidence of a crude association between maternal and newborn infection, also found in a systematic review of maternal infection in labour [28], suggesting a shared aetiology for some infections and highlighting the importance of caring for the woman and newborn synergistically.

Depression prevalence (4.1%) was lower than other LMIC studies that also used EPDS at 4–8 weeks postnatal. However, these studies showed considerable heterogeneity (range 4.9–50.8%) [29]. Telephone follow-up could provide a valuable tool to screen for postnatal depression and warrants further validation. We did not power our study to assess associations between maternal infection and depression or functioning, but our results suggest a trend in that direction, compatible with previous studies of maternal morbidity [29-32].

In our study, 66% of women and 88% of newborns with possible infection had sought health-facility care when interviewed, revealing the important proportion of cases that would be missed by a purely hospital based study. Telephone diagnosis of caesarean site infection achieved high specificity in Kenya and Tanzania [12, 13]. Telephone surveillance detected more cases of SSI than using patient case-notes or written surveys in high-income settings [33, 34]. Mobile telephone access was high in our study sample (97%), and we reached a high proportion of recruited women (90%), supporting the feasibility of telephone surveillance in comparable LMIC settings.

Strengths and limitations

Our study benefited from collecting data on specific components of standard infection definitions during the interview that were used in diagnosis algorithms, rather than relying on women’s or data collectors’ judgement. We collected data with a short recall period, reducing potential bias, and used symptom start dates to show infection distribution over time and estimate incidence rate. Although we recruited from two tertiary hospitals, we expect the population to be broadly representative of Dar es Salaam region where 94% of women are estimated to give birth in a facility and 17% by caesarean, similar to our study population.

The main limitation of this study is the unknown validity of the questionnaire to identify true cases of infection. We believe that the substantially increased rates of hospital readmission amongst women and newborns with telephone-based diagnosis of infections provide strong post-hoc support for the validity of our approach. Incidence of endometritis and pSBI and the association with caesarean childbirth are all closely consistent with other studies, lending further support to the results. However, we identified fewer cases of SSI than other studies, and we had two cases of neonatal sepsis extracted from hospital case-notes that were not subsequently reported at maternal interview. In addition, newborn deaths from infection were not captured, therefore true infection incidence may be higher than estimated. Furthermore, hospital case-notes were not located for 39 women, in some cases following admission of the baby, potentially reducing estimated infection incidence. It is possible that women who were unwell, or caring for a sick baby, were less likely to answer their telephones, also leading to an under-estimate of infection incidence. However, the use of a second telephone number belonging to a friend/relative, the repeated call attempts over seven days and the second interview at day-28 reduce this risk.

Conclusion

Our telephone surveillance study found a substantial and plausible rate of possible infection among mothers and newborns in urban Tanzania in the first month postnatal. Telephone interviews were feasible and identified cases that could be missed by hospital data collection alone. Results were consistent with previous studies, although further validation studies are needed. Therefore, this method of data collection shows promise for further use, both as a research tool and for routine medical practice. This could be of particular benefit during the current COVID pandemic, with concerns about reduced hospital attendance and the encouragement to work remotely. WHO does not recommend the use of routine postpartum antibiotics. Their use in this context showed no benefit and should be challenged. However, better implementation of pre-operative antibiotic prophylaxis for caesarean section is urgently required to mitigate the infection risk in mothers.

Telephone questionnaire–Day 28.

(DOCX)

Click here for additional data file.

Hospital case-note extraction form.

(DOCX)

Click here for additional data file.

Demographic, pregnancy and newborn factors by mode of delivery for 840 women and 829 liveborn babies with hospital record data by study hospital.

(DOCX)

Click here for additional data file.

Associations between potential risk factors and possible maternal postnatal infection.

(DOCX)

Click here for additional data file.

Associations between potential risk factors and possible newborn infection.

(DOCX)

Click here for additional data file.

15 Apr 2021

PONE-D-21-01978

Postnatal infection surveillance by telephone in Dar es Salaam, Tanzania: an observational cohort study

PLOS ONE

Dear Dr. Woodd,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 30 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Calistus Wilunda, DrPH

Academic Editor

PLOS ONE

Additional Editor Comments:

Footnote ‘b’ in tables 5 and 6 is not clear. Moreover, I could not identify footnote 'b' in Table 6.

Please use a consistent style for footnotes. In table 2, a special character is used but elsewhere letters are used.

RR can mean Risk ratio or rate ratio. Please specify. Given that you used Cox regression, why not report the effects as hazard ratios.

In reporting the results of association, especially in the abstract, please state explicitly the comparison group.

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study estimates rates of postnatal infection among women and infants in Dar es Salaam, Tanzania, using telephone surveillance. It demonstrates the feasibility of telephone surveillance for this purpose in Tanzania, and provides the first post-discharge estimates of maternal and newborn infection rates in this setting, as well as associated risk factors. It is clear, well-written, the methods and conclusions are sound, and it is a valuable addition to the literature on maternal and newborn health in sub-Saharan Africa.

Minor comments:

Line 72: Can any more information about the selected hospitals be provided? Are they public/private? What is their catchment area? How many hospitals of this size are there in Dar es Salaam?

Line 92: Given that one of the major limitations of the study is around the ability of the questionnaire to accurately identify infections, could you provide more details here on how the standard definitions were adapted? Are there any existing questionnaires for measuring postnatal infection that were considered but not used? If so, it would be helpful to discuss this here too.

Line 128: What was the frequency of discordant data, stillbirths and twins/triplets?

Reviewer #2: Line 203 - 28 early stillbirths occurred, did you include these in your final analysis?

Line 204 - between day 8-28 additional 6 babies died, did you include these numbers in you final analysis?

Line 217 - What do you mean by "weak evidence" of higher infection rates in women 25-29 years ( you make reference to table 5: [2.14 (1.12- 4.09): p=0.06]. How do you explain these p-value versus CI above 1.0?

Line 235: Maternal postnatal infection was associated with increased odds of possible newborn infection (crude Odds Ratio 2.74, 95%CI 1.16–6.48, p=0.02). Author should rephrase this statement or provide some explanation as well as discuss this in the section for discussion of results

Line 238-239: Please rephrase to provide easy readability

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Richard Mangwi Ayiasi

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

8 Jun 2021

Response to Editor's comments

The competing interests statement is updated as follows:

"I have read the journal's policy and the authors of this manuscript have the following

competing interests: SLW, AMK, AK, WM and WJG received personal salary funded by

The Soapbox Collaborative for their work on the study. SLW received a Research

Degree Travel Grant from LSHTM. AMR received salary from the UK Medical Research Council and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement. Other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials."

In tables 5 and 6 we have now combined the information into a single footnote:

Values imputed for variables with missing data, except for Preterm birth where the amount of missing data was considered too large to impute

We hope it is now clear that imputation was carried out for all variables except Preterm birth

We have updated table 2 to use a letter instead of a symbol for the footnote.

As suggested, we have changed the reporting to hazard ratios

We have now explicitly stated the comparison group for each association, in both the abstract, and the results section

Response to reviewers' comments

Reviewer 1:

The hospitals are two of the three public regional referral hospitals in Dar es Salaam, covering the districts of Ilala and Temeke. This has been reflected in the text.

For information, there are 28 hospitals at this level in Tanzania.

We adapted the infection definitions by removing all laboratory investigations and any clinical signs that could not be easily reported by the women, for example, temperature readings, abdominal tenderness, perineal wound redness. We were less rigid with some definitions e.g. superficial wound infection, to allow for these necessary omissions. A more detailed account is being written up elsewhere. A short sentence has been added to the manuscript.

"These definitions were adapted by the first author to include only symptoms and signs easily reported by the women."

We did not search extensively for other questionnaires, but from our work in this field, including a systematic review of maternal peripartum infection, we are not aware of any published, (validated) telephone questionnaires for this purpose.

Regarding twins and stillbirths: Among the 12 interviews with mothers of liveborn twins, only six record data on the second twin, partially due to a fault in the ODK programming.

Among mothers with hospital and telephone data, 28 have a baby who dies in the first 7 days. Of these, maternal cause-of-death reports are consistent with 7/8 of the hospital-recorded stillbirths. However, the hospital records miss 4 more stillbirths reported by mothers and at Temeke hospital no stillbirths are recorded, which we consider highly unlikely.

Reviewer 2:

Women giving birth in hospital and recorded in the delivery register were eligible for recruitment, including those with stillbirths. All recruited women who were reached for interview were included in the analysis of maternal postnatal infection.

Stillbirths contribute to the 28 deaths occurring up to day 7. Stillbirths were not included in the analysis of newborn infection.

As described in the methods, line 104, babies who died after day 7 contributed to the analysis (infection rate and analysis of associations) up to day 7 only.

Line 217 p=0.06: The p-value refers to the overall association between the three categories of age-group and infection rate rather than the 25-29 year group alone. We have rephrased the text to better reflect the result.

"There was also weak evidence of an association between women’s age-group and infection (p=0.06) with the highest infection rates occurring in women aged 25–29."

Submitted filename: Response to reviewers.docx

Click here for additional data file.

21 Jun 2021

Postnatal infection surveillance by telephone in Dar es Salaam, Tanzania: an observational cohort study

PONE-D-21-01978R1

Dear Dr. Woodd,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Calistus Wilunda, DrPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

23 Jun 2021

PONE-D-21-01978R1

Postnatal infection surveillance by telephone in Dar es Salaam, Tanzania: an observational cohort study

Dear Dr. Woodd:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Calistus Wilunda

Academic Editor

PLOS ONE