Background: Pre-eclampsia is the second leading cause of maternal death in Uganda. However, mothers report to the hospitals late due to health care challenges. Therefore, we developed and validated the prediction models for prenatal screening for pre-eclampsia. Methods: This was a prospective cohort study at St. Mary’s hospital lacor in Gulu city. We included 1,004 pregnant mothers screened at 16–24 weeks (using maternal history, physical examination, uterine artery Doppler indices, and blood tests), followed up, and delivered. We built models in RStudio. Because the incidence of pre-eclampsia was low (4.3%), we generated synthetic balanced data using the ROSE (Random Over and under Sampling Examples) package in RStudio by over-sampling pre-eclampsia and under-sampling non-preeclampsia. As a result, we got 383 (48.8%) and 399 (51.2%) for pre-eclampsia and non-preeclampsia, respectively. Finally, we evaluated the actual model performance against the ROSE-derived synthetic dataset using K-fold cross-validation in RStudio. Results: Maternal history of pre-eclampsia (adjusted odds ratio (aOR) = 32.75, 95% confidence intervals (CI) 6.59—182.05, p = 0.000), serum alkaline phosphatase(ALP) < 98 IU/L (aOR = 7.14, 95% CI 1.76—24.45, p = 0.003), diastolic hypertension ≥ 90 mmHg (aOR = 4.90, 95% CI 1.15—18.01, p = 0.022), bilateral end diastolic notch (aOR = 4.54, 95% CI 1.65—12.20, p = 0.003) and body mass index of ≥ 26.56 kg/m2 (aOR = 3.86, 95% CI 1.25—14.15, p = 0.027) were independent risk factors for pre-eclampsia. Maternal age ≥ 35 years (aOR = 3.88, 95% CI 0.94—15.44, p = 0.056), nulliparity (aOR = 4.25, 95% CI 1.08—20.18, p = 0.051) and white blood cell count ≥ 11,000 (aOR = 8.43, 95% CI 0.92—70.62, p = 0.050) may be risk factors for pre-eclampsia, and lymphocyte count of 800 – 4000 cells/microliter (aOR = 0.29, 95% CI 0.08—1.22, p = 0.074) may be protective against pre-eclampsia. A combination of all the above variables predicted pre-eclampsia with 77.0% accuracy, 80.4% sensitivity, 73.6% specificity, and 84.9% area under the curve (AUC). Conclusion: The predictors of pre-eclampsia were maternal age ≥ 35 years, nulliparity, maternal history of pre-eclampsia, body mass index, diastolic pressure, white blood cell count, lymphocyte count, serum ALP and end-diastolic notch of the uterine arteries. This prediction model can predict pre-eclampsia in prenatal clinics with 77% accuracy.
The research was a prospective cohort study at St. Mary's Hospital Lacor. This hospital is a private, not-for-profit hospital founded by the Catholic Church. It is located six kilometres west of Gulu city along Juba Road in Gulu district (Longitude 30 – 32 degrees East and Latitude 02 – 04 degrees North). St. Mary's Hospital Lacor is one of the teaching hospitals of Gulu University with a bed capacity of 482. It is staffed by specialists, medical officers, midwives, nurses, laboratory and radiology staff, and support and administrative staff. The hospital receives about three thousand six hundred antenatal mothers and conducts about six thousand deliveries annually [17]. Some mothers go to the hospital for delivery without prenatal care; others are referred from smaller health units. The mothers pay five thousand Uganda shillings (Ugx 5,000/ =) ($1.5) as the cost per visit. This cost is often waived for most mothers who cannot afford it. Normal labour and delivery cost fifteen thousand (Ugx 15,000/ =) (about $4.50), and Caesarean section costs twenty-five thousand (Ugx 25,000/ =) (about $7.5) Uganda shillings. Using Yamane's 1967 formula [18] for calculating sample size for cohort studies using finite population size: St. Mary's hospital Lacor receives approximately three thousand six hundred antenatal mothers annually. Since my study duration was 24 months, the limited population we could access was about 7,200 mothers. We doubled the sample size to take care of loss to follow-up. We targeted all pregnant women attending antenatal care at St. Mary's Hospital Lacor. In Uganda, the clinical guideline advocates for the first antenatal care to be sought by a pregnant mother up to 20 weeks of gestation [19]. While all expectant mothers attending antenatal care at St. Mary's hospital Lacor were eligible, we included gestational ages of 16 to 24 weeks and those who gave written informed consent to participate in the study. Those whose pregnancies were less than 16 weeks were given a return date for the recruitment, while those above 24 weeks or had molar pregnancies, intrauterine fetal death and anencephaly were excluded. We used consecutive sampling. We informed the mothers about the study during their morning health education meeting given to all mothers on arrival for prenatal care at the hospital. All the women who satisfied the inclusion criteria were approached and requested to provide informed consent. A research assistant administered questionnaire to capture their history and performed a physical examination. Some mothers were asked to give blood samples for full haemogram and liver and renal function tests. A few mothers (after the 1000th mother) did not undergo laboratory tests for logistical reasons. An obstetrician performed the uterine artery Doppler sonography. We recruited 1,285 pregnant mothers at 16–24 weeks from April 2019 to March 2020. All the mothers were of African ancestry at the end of the recruitment period. We followed up with the participants until September 2020. One thousand four (1,004) complete delivery records were obtained at the end of the study period. Seven hundred eighty-two (782) participants had laboratory blood tests (full haemogram, liver and renal function tests) done in addition to blood pressure readings, body mass index calculation and maternal history. Details are in Fig. 1. Flow chart of participants throughout the study The outcome was a combination of a blood pressure ≥ 140/90 mmHg and urine protein ≥ + 1 (pre-eclampsia) by delivery time. The data was pre-processed using Stata® version 15 and built models using RStudio version 4.1.3. Model 1 was built from second-trimester maternal history and physical examination findings, model 2 from the ultrasound and uterine artery Doppler indices, model 3 from a combination of maternal history, physical examination and ultrasound findings, model 4 from maternal laboratory tests, model 5 from a combination of laboratory tests with maternal history, and model 6 from the combination of all models. We included all variables, did a univariate analysis and got unadjusted p-values for every variable collected. Afterwards, we had all variables with p-values ≤ 0.20 or known risk factors for pre-eclampsia in a logistic regression model and removed the non-statistically significant predictors step-wise. Finally, we retained the independent risk factors for pre-eclampsia and used them to build the models of choice, one with the least number of predictors with a higher AUC. Because the incidence of pre-eclampsia was low (4.3%) [20], we generated synthetic balanced data using the ROSE package [21, 22] in RStudio by over-sampling pre-eclampsia and under-sampling non-preeclampsia. We got 383 (48.8%) for those diagnosed with pre-eclampsia and 399 (51.2%) for non-pre-eclampsia. Then, we evaluated the actual model performance against the ROSE-derived synthetic dataset using K-fold cross-validation in RStudio to obtain the AUC's accuracy, sensitivity, specificity and McFadden's pseudo R2. The variables were said to be independent risk factors for pre-eclampsia if their p-value < 0.05 in the model. The models, too, had a good fit if McFadden's value was between 0.2 – 0.4.
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