details the definitions used in the study for cases and controls for each race-ethnic group. The expanded case definition, sampling frame and 1:2 case: control ratio among Blacks resulted in 330 Black VPTB cases selected for chart abstraction and 343 controls [two times the 171.6 spontaneous VPTB cases anticipated based upon pilot data].
The linkage rate of prenatal screening and birth certificate data was 93%, and was slightly higher for Whites (95%) than for Blacks (92%) or Hispanic (91%). The linked file was used to generate the source population for this study. Maternal and paternal race-ethnicity information was missing for 1.5% and 6.1% of births, respectively. Missing paternal race-ethnicity was highest for births to Black mothers (13.9%, vs. 3.7% and 5.2% for births to White and Hispanic mothers, respectively).
A total of 346,456 births of all gestational ages met the race-ethnic group inclusion criteria for the study: 32.0% were White (n = 110,861), 62.7% Hispanic (n = 217,264) and 5.3% Black (n = 18,331) (). The prevalence of VPTB was higher among Blacks (2.5%) than Whites (0.8%) and Hispanics (1.1%) when gestational age was limited to <32 weeks. The prevalence for Blacks prior to 34 weeks gestation was 4.2%. After applying study exclusion criteria (, Steps 1 through 10), 1727 VPTB mother-infant pairs were identified (n = White, n = 1003 Hispanic and n = 330 Black). The chronological selection of White and Hispanic VPTBs stopped when the target of 385 maternal-infant pairs was reached (, Step 11). A random sample of 200 White, 253 Hispanic and 343 Black controls was selected from the same race-ethnic group-specific time period as cases. Among infants of Black women, 12% of cases and 10% of controls had missing or unknown paternal race-ethnicity, and 66% had paternal race reported as Black for both cases and controls. A total of five White, two Hispanic and nine Black VPTB case mothers had subsequent eligible VPTB deliveries within their respective cohorts, and none of the selected control mothers had subsequent VPTB deliveries.
Derivation of study population: very preterm births (VPTBs) selected for chart abstraction and controls from the linked prenatal screening livebirth cohort of 346 456 by race-ethnic group, California Very Preterm Birth Study
Ninety-eight percent of the linked prenatal screening livebirths were successfully linked to newborn screening records (data not shown); those that did not link included neonatal deaths that occurred prior to newborn screening. Maternal specimens of VPTB cases without newborn dried blood spots were included for maternal genotype analyses to increase statistical power and address biases that might arise from exclusion of early infant deaths (n = 142; , Step 2). In doing this, two earlier case pregnancies were identified for previously included mothers; therefore, the subsequent pregnancies were dropped (, Step 3).
Application of study inclusion/exclusion criteria to define spontaneous very preterm births (VPTBs) and type of specimens available by race-ethnic group, California Very Preterm Birth Study
Fewer than 2% (n = 19) of VPTB cases were excluded because of chart indication of multiple birth (n = 13) and/or stillbirth (n = 9) (, Step 4). An additional 3% (n = 30) were excluded because the chart-corrected gestational age was above our defined cut-offs for VPTB. The final assignment of gestational age was based on PNS ultrasound (n = 713), PNS LMP (n = 299), chart ultrasound (n = 70) or chart LMP (n = 42) (data not shown).
summarises the final classification of cases of spontaneous VPTB based on chart review. Forty-five percent (n = 492) of VPTBs were excluded because of likely causative medical conditions leaving slightly over half (55.0%, n = 601) of VPTBs that were spontaneous (i.e. with unknown cause). All cases have maternal specimens and 87% (n = 522) also have a newborn specimen. The proportion of spontaneous VPTBs was highest in Hispanics (58.8%), 54.8% in Blacks and lowest in Whites (51.6%). The main criteria for exclusion of cases were due to pre-eclampsia (~51% of all excluded), followed by intrauterine growth retardation (~22%), cervical cerclage (~15%) and pre-labour C-section for other medical indications (~8%). The proportion of exclusions due to use of assisted reproductive technologies was higher in Whites (7.2%) than Hispanics (2.0% or Blacks (1.4%). Excluded cases among Black women had a lower percentage of Mullerian anomalies but a higher proportion of sickle cell disease compared with other racial ethnic groups.
Selected medical characteristics of cases of spontaneous VPTBs are summarized in . In each race-ethnic group, approximately half of the spontaneous VPTBs had preterm labour and approximately half had preterm premature rupture of membranes, to the extent that this can be determined through hospital records. Pre-pregnancy obesity (defined as pre-pregnancy body mass index ≥ 30kg/m2) was the most common pre-pregnancy medical condition found among spontaneous VPTB cases; obesity was 1.5 times and three times more prevalent among Black women with spontaneous VPTB compared with Hispanic and White women, respectively. Chorioamnionitis, the most common medical complication of spontaneous VPTBs, affected approximately 40% of cases of spontaneous VPTB. Chlamydia and bacterial vaginosis were lower among White women compared with those who were Hispanic or Black.
Selected characteristics of cases of spontaneous very preterm birth (number and percent) by race-ethnic group, California Very Preterm Birth Study
summarises characteristics of the final sample of spontaneous VPTB cases and controls by race-ethnic group. The proportion of White spontaneous VPTB cases occurring before 26 weeks gestation (22.2%) was lower than in Black (30.5%) and Hispanic (29.0%) cases. The difference in proportions was larger when Blacks (similar to Hispanics and Whites) were limited to cases prior to 32 weeks gestation (42.8%, data not shown). Primiparity was more prevalent among White and Hispanic women with spontaneous VPTBs compared with Black women; the disparity in prevalence across race-ethnicity was similar among all VPTBs prior to selection of the first birth in the cohort. Male infants were somewhat more likely to be spontaneous VPTBs among White women only. The excess of White male births relative to controls was less pronounced among all White VPTBs (55.7%, data not shown) and was unaffected by the selection of the first birth in the cohort.
Selected maternal, pregnancy and infant characteristics (%) of spontaneous very preterm birth cases and controls, by race-ethnic group, California Very Preterm Birth Study