Prediction of stillbirth low resource setting in Northern Uganda

Stillbirth is the death of a fetus before birth after 20 weeks of gestation [1]. In the early twentieth century, stillbirth was any child who exhibits no sign of life by crying or breathing, or by pulsation in the cord at its attachment to the body of the child, or by beating of the heart and measuring more than 13 inches in length from the top of head to the heel at birth [2]. In the late twentieth century stillbirth was defined as any baby born at 24 weeks of gestation without a sign of life [3]. It can be classified as an early (24 – 27 weeks), late (28 – 36 weeks), or term ( 37 weeks) stillbirth [4].

The global prevalence of stillbirth is approximately 2% [5], with 0.3% occurring in the global north [6, 7], and more than 2% in the global south [5, 8‐10]. Women of Afro-Caribbean and Asian origin are more at risk of stillbirths [7, 11‐14] and this may be associated with racial disparities in accessing health care [12]. Incidence of stillbirth in Uganda is about 2.0%—3.6% [15, 16]. However, due to challenges in access to care and policies on death registration in the global south, most stillbirths are not registered [17].

When maternal obesity, smoking, chronic hypertension, antiphospholipid syndrome, type 2 diabetes, and insulin requirement are used in a prediction model risk calculator for stillbirth [18], it predicted stillbirths at 60—72% AUC at 75% sensitivity and close to 100% specificity [6, 7, 19]. When maternal history and fetal growth rates were added to maternal history without using the risk calculator, the discriminative performance of the model had a C-statistic of 0.80 [8].

There are limited number of tools built for risk-prediction models for stillbirth within sub-Saharan Africa. With the problems of access to hospital delivery and African ancestry being a risk factor for stillbirth, we set out to develop and validate a prediction model for stillbirth in Northern Uganda.

The Apgar score of zero within the first minute of birth at 24 + weeks was taken as stillbirth.

One thousand four (1004) complete delivery records were obtained at the end of the study period.. Of these, seven hundred eighty two mothers had laboratory blood tests done with 2.4% (19) stillbirths and 97.6% (763) live-births. Prevalence of stillbirth was 2.5% (25 out of 1004). There was 979 (97.5%) live births. Seven (28%) out of the 25 deaths occurred intrapartum. Two (8%) of the 25 mothers who lost their babies had a history of previous stillbirth. Two hundred eighty-one mothers were lost to follow-up. Details are found in Fig. 1.

The incidence rates for stillbirth were higher at lower gestation ages, as outlined in Table 1. There were 273 stillbirths per 10⁴ women weeks at < 28 weeks while only 3 stillbirths per 10⁴ women weeks at ≥ 37 weeks.

Mean maternal age was 26.3 years while 316 participants were first time mothers. Details in Table 2.

Average body-mass index (BMI) was 24.7, and prevalence of multiple pregnancy was 2.4%. Only 0.6% (6) of participants had prenatal hypertension at the time of recruitment. Details in Table 3.

Prevalence of anaemia in pregnancy was high with a mean haemoglogin level of 10.7 g/dL and haematocrit levels of 32.6%. Details in Table 4.

From demographic characteristics of our participants, the predictors of stillbirth were parity, age ≥ 35 years, history of abortion and personal history of preeclampsia. This predicted stillbirth with 65.8% accuracy, 82.4% sensitivity, 48.4% specificity and 71.9% AUC. In Niger state Nigeria, the predictors of stillbirth were maternal comorbidity, rural place of residence, multipara, bleeding during pregnancy, and non-cephalic fetal presentation [8]. Maternal employment was protective of stillbirth [8]. They predicted stillbirth with a C-statistic basic model = 0.80 (95% CI 0.78–0.83), and when ultrasound parameters were added the extended C-statistic model improved slightly to 0.82 (95% CI 0.80–0.83)[8]. In a case–control study in southern Ethiopia, the predictors of stillbirth were women with multiple pregnancy [aOR = 2.98, 95%CI: 1.39–6.36], having preterm birth [aOR = 2.83, 95%CI: 1.58– 508], having cesarean mode of delivery [aOR = 3.19, 95%CI: 1.87–5.44], having no ANC visit [aOR = 4.17, 95%CI: 2.38–7.33], and being hypertensive during pregnancy [aOR = 3.43, 95%CI: 1.93–6.06].[22]. However, these women were recruited after they had given birth. In clinical settings in low resource settings one can use the demographic characteristics above as predictors to identify up to two-thirds of mothers at risk of having stillbirth. Despites the model’s sensitivity of 82.4%, the model’s specificity of 48.4% is low. One will have to put more than twice the number of women identified as at risk of stillbirth in order to get the two thirds of women who will actually get stillbirth.

Combination of uterine artery Doppler indices and maternal history predicted stillbirth by 67.6% accuracy, 75.8% sensitivity and 69.9% AUC. This may be comparable to Akolekar et al.[19] who predicted 55% of all stillbirths, including 75% of those due to impaired placentation and 23% of those that were unexplained or due to other causes, at a false-positive rate of 10% using maternal history and uterine artery Doppler indices. Ultrasound examination is not compulsory in Uganda[23]. It is reserved for a few referral centers, teaching hospitals and private hospitals[24, 25]. Majority of the mothers go through their gestation period without performing a single ultrasound scan.

We predicted stillbirth by 75.0% AUC with 68.1% accuracy, 69.1% sensitivity and 67.1% specificity. This was comparable to the stillbirth-risk calculator [18] validated in Austria at 72% AUC [6]. In the United Kingdom, stillbirth detection rates ranged from 28 to 48% with an AUC of 55.0% to 65.8% even after allowing a 10% false positive rate [7, 19]. In Australia, the detection rate for stillbirth was 45%, with an AUC ranging from 59 to 84% [26]. Similarly, in the United States of America, the detection rate for stillbirth has been 64%—66% AUC [27].

Mastrodima et al. [28] used maternal factors, PAPP-A, Doppler pulsatility index and ductus venosus pulsatility index for veins (DV-PIV), and predicted 40% of all stillbirths and 55% of those due to impaired placentation, at a false-positive rate of 10%. Within the impaired-placentation group, the detection rate of stillbirth < 32 weeks’ gestation was higher than that of stillbirth ≥ 37 weeks (64% vs 42%). This makes the study compare favorably to those conducted in global north. Perhaps the differences seen is due to the differences in the population itself and the technology used for the prediction of stillbirth.

In places where ultrasound or laboratory services are not available, the predictors of stillbirths are history of abortion, personal history of preeclampsia, maternal age ≥ 35 years and parity. These variables predict stillbirth by 71.9% AUC with 68.5% accuracy, 82.4% sensitivity and 48.4% specificity.