Study design
We used a case–control study design nested within a larger prospective cohort study. All women delivering in the hospital were included in the source population, from which 20 % were randomly selected to be in the referent population. This 20 %, i.e. the referent population, was selected at the time of their admission to the hospital using a lottery technique. All women experiencing an intrapartum stillbirth during the study period were included in the case population. Any antepartum stillbirth occurring in the referent population was excluded from this study; while any intrapartum stillbirth that occurred in the referent population was excluded from that population and re-categorized for inclusion in the case population. The sample size of this study was based on calculations used in the larger prospective cohort study, which aimed to detect a 20 % reduction in perinatal mortality with a statistical power of 80 % and a level of significance of 5 %.
Ethical approval for this study was obtained from the Institutional Review Committee at Paropakar Maternity and Women’s Hospital, the Nepal Health Research Council (reg. 37/2012) and from Uppsala University (Sweden) (dnr. 2012/267), as part of a larger cohort study evaluating the impact of a Helping Babies Breathe quality improvement cycle on perinatal mortality [
26]. The study was registered as clinical trial under the registration number: ISRCTN 97846009. The protocol for the study can be accessed from
http://bmcpediatr.biomedcentral.com/articles/10.1186/1471-2431-12-159. Written consent was received from each of the study participants prior to their inclusion.
Data collection
A surveillance system was set up by recruiting 12 female surveillance officers to be stationed in the admission, delivery, and postnatal units. Any woman admitted to the hospital for delivery was marked in the surveillance registry. From this sampling frame, study participants were randomly selected using a lottery technique. Specifically, an opaque jar with 100 balls was kept in the admission unit, of which 80 were white and 20 were yellow. Upon each admission, a ball was drawn from the opaque jar; if a yellow ball was selected, the woman was enrolled into the study as part of the referent population. When a woman was selected as part of the referent population, she was tracked from the point of admission through her discharge to assess labor progression and birth outcomes.
The surveillance team in the delivery unit observed all deliveries together with referent population. When intrapartum stillbirth occurred in the delivery unit, the surveillance officers enrolled the woman with intrapartum stillbirth into the study as part of the case population. Woman in case population was tracked from delivery through her discharge. Women in case population (intrapartum stillbirth) had also received the same rigorous observations during labor and birth as the women in referent population. Information collected for women in case and referent population remained the same. For both the referent and case populations, information on parity, previous obstetric and medical history, care received during the current pregnancy, obstetric or medical complications during this pregnancy, and intrapartum care was retrieved from clinical record forms. Surveillance team members conducted interviews at the time of discharge with each woman using a questionnaire designed to assess the woman’s social, demographic and household information.
After receiving the completed clinical record and interview forms from the surveillance officers, a research manager checked each form for completeness. Additionally, 10 % of clinical record forms were checked against the primary data source to ensure data accuracy. Data entry officers reassessed the completeness of all forms, recoded open-ended response questions, and entered the data from each checked form into a CS-Pro database. To prevent data loss, indexing of all collected forms was performed. After data entry and data cleaning in the CS-Pro database was completed, the dataset was exported to SPSS 17 for data analysis.
Variables
Intrapartum stillbirth was defined as the delivery of any fetus after 22 weeks of gestation, or with a birth weight more than 500 g, who had detectable fetal heart sounds upon admission, but died during the intrapartum period and thus had an Apgar score of 0 at 1 and 5 min, without signs of maceration. Intrapartum stillbirth cases were retrieved from the clinical journal [
1].
Antepartum stillbirth was defined as the delivery of any non-viable fetus after 22 weeks of gestation, or with a birth weight more than 500 g, with an Apgar score of 0 at 1 and 5 min and signs of maceration, or absent fetal heart sound before the initiation of labor [
1].
Maternal age was categorized into five-year intervals.
Maternal education was categorized into two groups as women who had 5 years or less than 5 years of education (primary education), and those who had six or more years of education (secondary education or higher).
Ethnicity was categorized into groups according to the social caste system within Nepal [
28] as most advantaged (Brahmin/Chettri); relatively advantaged Janajatis (Newar, Gurung and Thakali); relatively disadvantaged Janajatis; relatively disadvantaged non-Dalit; most disadvantaged (Dalit and Muslim).
Wealth index was used as a measure of socioeconomic position and constructed according to the nationally representative health surveys (Demographic Health Surveys), to compare socioeconomic inequalities [
29,
30]. During interviews with each mother, data was collected on ownership of durable assets (e.g. car, refigerator, bicycle, radio, television), housing characteristics (e.g. number of rooms, dwelling floor and roof materials, toilet facilities), and access to services (e.g. electricity supply, drinking water source). Using the scores from the first principal component analysis, a wealth index (asset index) was constructed. Based on the value of this index, individuals were sorted and population quintiles were established using cut-off values. These quintiles were then ranked from bottom to top as poorest, poorer, middle, richer and richest [
31].
Antenatal care attendance was determined based on whether a mother attended any antenatal care (ANC) visits during which she received a clinical examination, counseling, and medication (if needed) from a skilled provider as per guidelines. ANC was categorized into two groups as those who attended at least one ANC visit, and those who did not receive any ANC at all.
Parity was based on the number of times a woman had previously given birth after the age of viability, i.e. 22 weeks, including both live and still births [
32]. Parity was categorized into three groups including primiparous, multiparous (1–2) or multiparous (3 or more).
Previous stillbirth was categorized as whether the women had any stillbirth in a previous pregnancy(s), or not.
Antepartum hemorrhage was defined as vaginal bleeding prior to the onset of labor. This was categorized into two groups as those having any antepartum hemorrhage, or none.
Hypertensive disorder of pregnancy was defined as a maternal diastolic blood pressure of 90 mmHg or more in two consecutive assessments, which were at least four hours apart, during pregnancy. This was categorized as those having the condition in the current pregnancy, or not.
Medical complication during pregnancy was considered present in women having diabetes mellitus, severe anemia (Hb <7 gm/L), or epilepsy during the current pregnancy.
Multiple birth included women pregnant with more than one fetus.
Obstetric complication during delivery was defined as any complication that a woman had during the intrapartum period [
33], including:
Hypertensive disorder
Classified by maternal diastolic blood pressure greater than or equal to 90 mmHg in two separate recordings
Mal-presentation
Presentation of the fetus in any position besides vertex, i.e. with the top of the head appearing first
Prolonged labor
Cervical dilation that does not move beyond 4 cm after eight hours of regular contractions, or cervical dilation lying to the right of the alert line on the partogram; and
Prolapsed cord
Characterized by the presence of the umbilical cord in the birth canal below the fetal presenting part, or at the vagina following the rupture of membranes.
Fetal Heart Rate Monitoring (FHRM) per protocol was considered adequate when the fetal heart rate was measured at least every half an hour using the auscultation technique, during the intrapartum period. Any labor in which fetal heart rate was not monitored within every half an hour was categorized as non-adherent to protocol.
Adherence to partogram use was considered adequate when the partogram was used, i.e. filled in for the progress of cervical dilation and descent of the head, every half an hour to assess the progression of labor. Any case where labor progression was not adequately monitored using the partogram was categorized as non-adherent.
Gestational age of the baby was categorized into two groups as preterm or term according to the following defintitions:
Preterm birth
which included babies born before 37 completed weeks of gestation, estimated by the date of the mother’s last menstrual period or based on clinical examination of the newborn
Term birth
which included babies who were born at, or after, 37 completed weeks of gestation, estimated by the mother’s last menstrual period or based on clinical examination of the newborn.
Weight for gestational age at birth was categorized into two groups as small- or appropriate- for gestational age according to the following definitions:
Small-for-gestational age (SGA)
which included babies whose birth weight was less than the 10
th percentile according to the appropriate gestational age and sex-specific reference population standards [
34]
Appropriate for gestational age (AGA)
which included babies whose birth weight was greater than or equal to the 10
th percentile according to the appropriate gestational age and sex-specific reference population standards [
34].
Statistical analysis
The comparison of demographic and obstetric characteristics of the women in the referent and case populations was performed using Pearson’s chi-square test for categorical variables, along with Fisher’s exact test. Means and medians of maternal age were also compared. The following variables were compared between the case and referent populations: maternal age (categorical), maternal education, ethnicity, wealth quintile, ANC attendance, parity, previous stillbirth, antepartum hemorrhage, hypertensive disorder during pregnancy, medical disorder during pregnancy, multiple births, obstetric complications during labor, FHRM per protocol, use of partogram, mode of delivery, sex of baby, weight for gestational age at birth, gestational age of baby and a combination variable including both weight for gestational age and gestational age at birth.
Univariate logistic regression was used to determine the level of association between different demographic/obstetric characteristics and intrapartum stillbirth that showed a difference (p < 0.001) in the chi-square analysis, between the referent and case populations. Multivariate logistic regression analysis was then conducted to determine the level of association between the demographic or obstetric characteristics and intrapartum stillbirth for those with a significant association in the univariate model.
To the greatest extent possible, missing data was minimized; however, there were missing data for some background characteristics of the mothers. We used the multiple imputation method to deal with this data that was missing at random [
35].