Incidence and risk factors of preterm birth in a rural Bangladeshi cohort

We analyzed prospectively collected data from a large community-based cluster-randomized trial conducted in Sylhet district of Bangladesh. Data for our study were primarily collected to evaluate the impact of two regimens of umbilical cord cleansing - single-day vs. 7-day - with 4.0% chlorhexidine solution on all-cause neonatal mortality and incidence of cord infections [11, 12].

Details of the study designs, interventions, delivery strategies and the map of the area have been published elsewhere [11, 12]. Briefly, CHWs followed a complete map of all households and thus prepared a complete list of all married women of reproductive age (MWRA) through house-to-house visitation and recorded their names, addresses and pregnancy status. The list was updated and new pregnancies were identified every two months by conducting home visits. All newly identified pregnant women were invited to participate in the study and explained the study procedures. Those agreeing to participate gave informed oral consent and provided data on age, parity, date of last menstrual period, literacy, a brief pregnancy history, and socio-economic information about the household.

All enrolled women were provided with a package of maternal and newborn health interventions, delivered by CHWs through two antenatal home visits. The first session was conducted at the time of enrolment at 12–16 weeks of pregnancy and the second occurred at approximately 32 weeks of pregnancy. The intervention package included a clean delivery kit (CDK), messages on birth and newborn care preparedness (BNCP), and advice on essential newborn care (immediate breastfeeding, thermal care and clean cord care) and on neonatal danger sign recognition and care-seeking [11, 13]. At each visit, information was collected by CHWs on status of birth and neonatal care preparedness, antenatal care (ANC), complications during pregnancy and care seeking for those complications. BNCP included practice of the following 6 steps: 1) selection of birth attendant, 2) selection of newborn care personnel, 3) arrangement for three pieces of cloth for drying/wrapping of the newborn, 4) arrangement for transport for any emergency need, 5) savings for management of complications, and 6) having a CDK for use during delivery.

All reported live births within the study area for which data was available on the first day of the last menstrual period (LMP) were included in this study. Reported stillbirths and abortion (spontaneous, induced or therapeutic) were excluded. Pregnancies terminated before 28 weeks of gestation were defined as miscarriage/abortion. A stillbirth was defined as an infant born without any signs of life (no spontaneous crying, breathing, and/or movement) at 28 weeks of gestation or later.

Socio-demographic and economic information (women’s age at delivery, educational attainment of women and their husbands, basic housing construction, household belongings, religion) and previous pregnancy history were collected by CHWs using a structured instrument in face-to-face interviews during the enrolment visit. Relevant data on antenatal care seeking, compliance with BNCP, consumption of supplied iron tablets, TT immunization dosage and antenatal complications (history of fever, severe abdominal pain, swelling of hand, leg or face, vaginal bleeding, convulsion, severe headache, blurring of vision) were also collected from all women during BNCP visits or the first postpartum visit. Compliance with BNCP was categorized as “fully compliant” (woman reported practice all 6 of the above-mentioned steps), “partially compliant” (1–5 steps), or “non-compliant” (0 steps). CHWs measured the mid upper arm circumference (MUAC) of the enrolled mothers during enrollment visits. Data on antenatal complications (except fever) were self-reported by respondent women. CHWs measured axillary temperature from women who reported having fever during the interview.

The primary outcome was preterm birth as defined by the World Health Organization as: “Any birth before 37 completed weeks of gestation or fewer than 259 days since the first day of the women’s LMP” [14]. Gestational age at birth was computed from the difference between the date of pregnancy outcome and the date of the first day of the LMP recorded at enrolment. Date of first day of the LMP was determined through maternal report to a CHW during a two-monthly pregnancy surveillance visit at the household, when the CHW asked the pregnant women to recall LMP with the assistance of calendars and memory aids. Women for whom no date of LMP was estimated after several attempts using various approaches were excluded from analysis. Date and type of pregnancy outcome was recorded by a CHW on her first visit after women delivered, usually within 24 hours or as soon as possible after birth.

CHWs received 6 weeks of classroom-based and hands-on supervised training. These training sessions followed a structured curriculum including skills development for behavior change communication, provision of BNCP and essential newborn care, clinical assessment of neonates, and identification and management of sick newborns using an algorithm adapted from Integrated Management of Childhood Illness. Quality of data collected by CHWs was ensured through direct supervision by respective Field Supervisors. Supervisory visits and standardization exercise sessions were organized routinely to ensure quality of data collected. Every reported neonatal death was confirmed by a repeat visit to the household by a supervisory staff. A sample (5%) of newborns who survived the neonatal period was revisited for quality assurance of vital status reporting by CHWs.

CHWs submitted data forms to their supervisor, who checked the forms for completeness and consistency. Data entry system was custom-designed with built in range and consistency checks. Field verifications were conducted to resolve identified inconsistencies and incompleteness if required.

Births at ≥37 weeks were classified as term births. Preterm births were sub-categorized as: 1) Very preterm (28 – 31 weeks of gestation), 2) Moderate preterm (32–34 weeks of gestation) and 3) Late Preterm (35–36 weeks of gestation). We estimated the incidence of preterm birth by dividing all live preterm births, whether singleton, twin or higher order multiples, by all live births in the population; 95% confidence intervals (CI) were calculated for the estimated proportion of preterm birth incidence.

Based on published reports and considering biological plausibility, we categorized, a priori, the potential risk factors for preterm birth into three groups: 1) Proximal factors: antenatal care seeking and antenatal complications during the index pregnancy; 2) Intermediate factors: previous pregnancy history; 3) Distal factors: socio-demographic characteristics. We constructed a wealth index score [15] for each household by employing principal component analysis of basic housing construction materials (i.e., materials used to construct the walls, roof, and floor of houses), sources of water, sanitation facilities and household belongings.

Covariates showing moderate strength of association (P <0.10) in bivariate analysis were included in multivariate models, which were constructed in a three-step sequence starting with proximal factors [Model1] and progressively adding previous pregnancy/birth information [Model2] and thereafter distal/socio-demographic factors) [Model3]. The association (risk ratio) between potential risk factors and preterm birth was modeled using binomial regression with a log link function; generalized estimating equations with exchangeable correlation structure were used to adjust standard errors to account for clustering [16, 17]. In case of convergence failure, poisson models with robust standard error estimation were used [18, 19]. Imputation of missing data was done using the “hotdeck” method by cluster [20]. Data were analyzed by using STATA (version 11) statistical package [21].

We received ethical approval for the study from the Institutional Review Board of Johns Hopkins Bloomberg School of Public Health and from the Ethical Review Committee of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). The study was registered at ClinicalTrials.gov (NCT00434408).

The majority (61.7%) of respondents was in the 20–29 year age group and most of them (95.5%) were Muslim (Table 1). More than half (51.9%) of the respondent, and 43.9% of their husbands had primary or higher level of education. Higher education level [5 or more years of schooling (Primary plus)] of both the mother [Relative Risk (RR): 0.92; 95% CI: 0.88, 0.97] and her husband (RR: 0.94; 95% CI: 0.89, 0.99) was associated with lower risk of preterm birth compared to lower education level. Compared to the highest wealth quintile group, the lowest quintile group of respondents had a 37.0% higher risk of preterm delivery (RR: 1.37; 95% CI: 1.26, 1.49).

The index pregnancy was fourth or higher order for 42.4% of respondent women (Table 2). Compared to women having fourth or higher birth order, primigravid women had 9.0% lower risk of delivering a preterm baby (RR: 0.91; 95% CI: 0.84, 0.98). From 18.2% of women, a history of child death was reported, which was associated with higher risk of preterm birth (RR: 1.05; 95% CI: 1.01, 1.10). A woman who delivered twins or triplets was at about 1.6-fold higher risk of preterm delivery (RR: 1.61; 95% CI: 1.49, 1.74) compared to a woman who delivered a singleton baby. Among all live births reported, 52.0% were boys; a female baby was 9.0% less likely to be preterm than a male baby (RR: 0.91; 95% CI: 0.88, 0.95).

Most women (57.3%) sought antenatal care at least once, 79.5% reported receiving any dose of tetanus toxoid (TT) immunization, and 89.9% consumed iron-folic acid (IFA) during the index pregnancy (Table 3). About one third (32.0%) of women practiced all six steps for BNCP while another 58.6% practiced partially. Antenatal complications of pregnancy were reported by 1.6% of women.

Bivariate association of each of these proximal factors with preterm birth risk is presented in Table 3. Compared to no visit at all, any ANC visit was associated with 25.0% lower risk of preterm birth (RR: 0.75; 95% CI: 0.72, 0.78). Risk of preterm delivery was also lower for women who undertook all BNCP steps (RR: 0.30; 95% CI: 0.29, 0.32) and women who received any dose of TT vaccine during pregnancy (RR: 0.90; 95% CI: 0.86, 0.94). Almost one-fifth (18.9%) of the respondents had a MUAC <214 mm. Maternal MUAC was inversely associated with preterm birth risk; for each cm increase in average MUAC measures, risk of preterm birth was 5.6% lower (95% CI: 4.8% - 6.5%). Women who reported any antenatal complication had 16.0% higher risk of preterm delivery compared to women who did not report any antenatal complication (RR: 1.16; 95% CI: 1.02, 1.35). Itemized risk analysis for each of the antenatal complications is presented as Additional file 1 : web-table S1 (available online).

Risk estimates from bivariate analyses for proximal factors, specifically for any antenatal visit, any antenatal complication, birth preparedness steps, and any dose of TT immunization, were not changed significantly after adding all proximal factors into the multivariate Model-1 (Table 4). Association of preterm birth with low MUAC was attenuated while the risk associated with IFA consumption was increased in magnitude relative to the estimate in bivariate analysis. In model-2, intermediate factors were added to proximal factors and estimated risk of preterm birth was 8% higher (RR: 1.08; 95% CI: 1.03, 1.13) among women who had a previous child death. Women having lower birth order had lower risk of preterm birth. Also a female child appeared to have 7.0% lower risk (RR: 0.93; 95% CI: 0.90, 0.96) of being born preterm, compared to a male child. In model-3, distal factors were added; risk estimates were attenuated but remained significant for women with lower MUAC and women consuming IFA during pregnancy, relative to the first model. Longer periods of iron-folic acid intake were associated with higher risk of preterm birth (for less than 2 months RR: 1.32; 95% CI: 1.21, 1.45; for 2–6 months, RR: 1.33; 95% CI: 1.24, 1.44). Risk of preterm birth remained high, but was attenuated, for women who continued to receive IFA supplementation beyond 6 months (RR: 1.28; 95% CI: 1.11, 1.47). Additionally, women who had a previous child death, had multiple pregnancy, had any antenatal complication and were in the poorest quintile were at significantly higher risk of preterm delivery, while at least one ANC visit, primigravida, adoption of all 6 steps for BNCP, education at primary or higher level, and TT immunization provided protection.