Adverse birth outcomes and their clinical phenotypes in an urban Zambian cohort

Abstract

Background: Few cohort studies of pregnancy in sub-Saharan Africa use rigorous gestational age dating and clinical phenotyping. As a result, incidence and risk factors of adverse birth outcomes are inadequately characterized. Methods: The Zambian Preterm Birth Prevention Study (ZAPPS) is a prospective observational cohort established to investigate adverse birth outcomes at a referral hospital in urban Lusaka. This report describes ZAPPS phase I, enrolled August 2015 to September 2017. Women were followed through pregnancy and 42 days postpartum. At delivery, study staff assessed neonatal vital status, birthweight, and sex, and assigned a delivery phenotype. Primary outcomes were: (1) preterm birth (PTB; delivery <37 weeks), (2) small-for-gestational-age (SGA; <10 ^th percentile weight-for-age at birth), and (3) stillbirth (SB; delivery of an infant without signs of life). Results: ZAPPS phase I enrolled 1450 women with median age 27 years (IQR 23-32). Most participants (68%) were multiparous, of whom 41% reported a prior PTB and 14% reported a prior stillbirth. Twins were present in 3% of pregnancies, 3% of women had short cervix (<25mm), 24% of women were HIV seropositive, and 5% were syphilis seropositive. Of 1216 (84%) retained at delivery, 15% were preterm, 18% small-for-gestational-age, and 4% stillborn. PTB risk was higher with prior PTB (aRR 1.88; 95%CI 1.32-2.68), short cervix (aRR 2.62; 95%CI 1.68-4.09), twins (aRR 5.22; 95%CI 3.67-7.43), and antenatal hypertension (aRR 2.04; 95%CI 1.43-2.91). SGA risk was higher with twins (aRR 2.75; 95%CI 1.81-4.18) and antenatal hypertension (aRR 1.62; 95%CI 1.16-2.26). SB risk was higher with short cervix (aRR 6.42; 95%CI 2.56-16.1). Conclusio ns: This study confirms high rates of PTB, SGA, and SB among pregnant women in Lusaka, Zambia. Accurate gestational age dating and careful ascertainment of delivery data are critical to understanding the scope of adverse birth outcomes in low-resource settings.

Keywords: Zambia; adverse birth outcomes; pregnancy; preterm birth; small for gestational age; stillbirth; sub-Saharan Africa.

Figure 1.. ZAPPS cohort participant flowchart.

ANC, antenatal care; UTH-WNH, Women and Newborn Hospital of University Teaching Hospital.

Figure 2.. Preterm birth, very preterm birth, small for gestational age, very small for gestational age, and stillbirth among participants retained at delivery in ZAPPS cohort.

Among ZAPPS cohort participants retained at delivery, 15% (181/1216) were preterm (PTB), 8% (92/1216) were very PTB, 18% (207/1159) were small for gestational age (SGA), 7% (80/1159) were very SGA, and 4% (53/1209) were stillborn (SB). *11 preterm births (^9 of which were very preterm), one term stillbirth, and 20 preterm stillbirths (^18 of which were very preterm) were either outside the gestational age threshold for INTERGROWTH-21 ^st calculation of SGA, or were missing birthweight at delivery. Figures created with: EulerAPE.

Figure 3.. Parturition phenotypes among ZAPPS participants with preterm delivery.

Of participants who underwent preterm delivery (n=181) in the ZAPPS cohort, 120 of them were spontaneous and 56 were indicated. This figure presents the frequencies of primary conditions present in spontaneous preterm deliveries, primary indications for indicated preterm deliveries, and the overall frequency with 95% confidence intervals of key conditions in each group. Gray bars represent missing values. APH, antepartum hemorrhage; OB HX, obstetrical history.

Figure 4.. Predicted probability of preterm birth <37 weeks by mid-trimester cervical length.

Among ZAPPS cohort participants with a cervical length measured by ultrasound in the second trimester (n=1081), the probability of preterm birth <37 weeks decreased with increasing cervical length. PTB, preterm birth; RR, relative risk; CI, confidence interval.

Figure 5.

Kaplan-Meier survival curves by ( a) prior preterm birth, ( b) short cervix (<25mm), and ( c) twin gestation. Survival curves are presented for participants with increasing numbers of prior preterm birth, those with cervical length <25mm compared to ≥25 mm, and those with twin compared to singleton gestation. The dashed vertical line represents a gestational age of 37 weeks, the threshold for preterm versus term delivery. EGA, estimated gestational age; PTB, preterm birth.