Materials and Methods
This is a retrospective cohort study of 1,604,386 pregnancies of women between 34 and 40 weeks’ gestation in the state of California during the years of 2005-2008. International Classification of Diseases , 9th version (ICD-9), codes were used to identify 5545 pregnancies complicated by ICP. Our control group consisted of pregnant women without ICP at the same gestational week. Both groups excluded multiple gestations and congenital anomalies to avoid confounders. Approval from the institutional review boards at Oregon Health and Science University and the state of California was obtained.
The data used for outcome analysis were obtained from the California Vital Statistics Birth Certificate Data, California Patient Discharge Data, Vital Statistics Death Certificate Data, and Vital Statistics Fetal Death File. These data are part of the public record and deidentified; therefore, informed consent was not required. The state of California maintains linked maternal and infant data sets, starting 9 months prior to delivery and up to 1 year after delivery. The data sets also include infant birth records and all hospital admissions up to 1 year of life. A unique record linkage number is assigned to the mother-infant pair by the California Office of Statewide Health Planning and Development Healthcare Information Resource Center under the state of California.
For each week of gestation, the following outcomes were assessed for both the ICP and control subjects: the risk of stillbirth defined as fetal demise at or after 20 weeks’ gestation, the risk delivery represented by the risk of infant death following delivery at a given week of gestation, and the composite mortality risk of expectant management for 1 additional week.
The risk of stillbirth was calculated by dividing the number of stillbirths that occurred at a particular week of gestation by the number of ongoing pregnancies at that particular gestation. Composite mortality risk of expectant management was calculated by combining the risk of stillbirth at a given gestational age week plus the risk of infant death if delivery occurs at the subsequent week of gestation per 10,000 fetuses at risk.
χ 2 tests were used for statistical analysis. A value of P < .05 was considered statistically significant. The data are also presented as odds ratios (ORs) with 95% confidence intervals (CIs) with an assumption of statistical significance if the 95% CI did not contain 1.
Results
Of 1,604,386 singleton pregnancies without congenital anomalies, 5545 pregnancies in the cohort were complicated by ICP with a calculated incidence of 0.35%. Women with ICP were more likely to be Hispanic or Asian, older, and have other comorbidities such as chronic hypertension, diabetes, and gestational diabetes ( Table 1 ).
| Characteristics | ICP (n = 5545) | Control (n = 1,598,841) | |||
|---|---|---|---|---|---|
| n | % | n | % | P value | |
| Ethnicity | < .001 | ||||
| White | 1261 | 21.2 | 499,457 | 27.0 | |
| African American | 120 | 2.0 | 90,495 | 4.9 | |
| Hispanic | 3448 | 58.1 | 1,005,661 | 54.4 | |
| Asian | 1027 | 17.3 | 218,416 | 11.8 | |
| Other | 80 | 1.4 | 34,890 | 1.9 | |
| Nulliparous | 2376 | 40.1 | 734,283 | 39.7 | .556 |
| Chronic hypertension | 86 | 1.5 | 18,824 | 1.0 | .001 |
| Diabetes | 97 | 1.6 | 12,980 | 0.7 | < .001 |
| Gestational diabetes | 652 | 11.0 | 116,583 | 6.3 | < .001 |
| Maternal age >35 y | 1256 | 21.2 | 315,916 | 17.1 | < .001 |
| Maternal age <20 y | 327 | 5.5 | 173,480 | 9.4 | < .001 |
| Public insurance | 2900 | 48.9 | 890,568 | 48.1 | .251 |
| Education >12 y | 2891 | 46.0 | 808,940 | 45.0 | .114 |
| Limited prenatal care (<5 prenatal visits) | 221 | 3.5 | 63,558 | 3.5 | .915 |
The risk of stillbirth was higher in women with ICP than in our control group at each gestational age between 34 and 40 weeks compared with our control group (overall this was 63.8 vs 21.2 per 10,000; P < .001) with a peak at 40 weeks’ gestation. The increased risk of stillbirth remains statistically significant in ICP between 32 and 40 weeks’ gestational age (OR, 2.17; P = .004), even when controlling for confounders including race, maternal age, chronic hypertension, diabetes, gestational diabetes, nulliparous status, and limited prenatal care.
The risk of delivery represented by the risk of infant death is lowest at 36 weeks and increased thereafter in women with ICP. In contrast, in women without ICP, the risk of delivery reaches a nadir at 39 weeks (9.8 per 10,000; 95% CI, 9.3–10.3) before beginning to rise again ( Table 2 ).
| Variable | Stillbirth per 10,000 ongoing pregnancies (95% CI) | Infant death per 10,000 live births (95% CI) | ||
|---|---|---|---|---|
| GA, wks | ICP | Control | ICP | Control |
| 34 | 2.3 (0.0–6.2) | 1.7 (1.5–1.9) | 22.2 (10.2–34.2) | 42.1 (41.1–43.0) |
| 35 | 4.4 (0.0–9.9) | 1.9 (1.7–2.1) | 26.9 (13.5–40.3) | 27.1 (26.4–27.9) |
| 36 | 6.8 (0.0–13.8) | 2.1 (1.9–2.3) | 4.7 (0.0–10.5) | 22.9 (22.2–23.6) |
| 37 | 8.0 (0.0–16.0) | 2.3 (2.1–2.5) | 12.3 (2.4–22.3) | 18.0 (17.3–18.6) |
| 38 | 4.7 (0.0–11.9) | 3.2 (2.9–3.5) | 13.7 (1.5–26.0) | 11.8 (11.3–12.3) |
| 39 | 11.1 (0.0–25.1) | 4.2 (3.8–4.5) | 18.3 (0.5–36.2) | 9.8 (9.3–10.3) |
| 40 | 26.5 (0.0–56.5) | 5.8 (5.2–6.4) | 22.5 (0.0–50.2) | 10.4 (9.8–11.0) |
Among women with ICP, the risk of delivery is lower than the risk of expectant management at 36 weeks’ gestation (4.7 per 10,000 [95% CI, 0.0–10.5] vs 19.2 per 10,000 [95% CI, 7.6–30.8]). After 36 weeks’ gestation, the risk of expectant management remains higher than delivery and continues to rise at each week of gestation thereafter ( Figure ).
When the same comparison was made in the control group, the rate of mortality was lower in the expectant management group at 37 weeks and earlier, no different at 38 weeks, and greater in the expectant management group at 39 weeks of gestation ( Table 3 ).
| Variable | ICP (n = 5545) | Control (n = 1,598,841) | ||
|---|---|---|---|---|
| GA, wks | Infant death per 10,000 live births (95% CI) | Risk of expectant management per 10,000 (95% CI) a | Infant death per 10,000 live births (95% CI) | Risk of expectant management per 10,000 (95% CI) a |
| 34 | 22.2 (10.2–34.2) | 29.2 (15.5–43.0) | 42.1 (41.1–43.0) | 28.8 (28.0–29.6) |
| 35 | 26.9 (13.5–40.3) | 9.1 (1.4–16.9) | 27.1 (26.4–27.9) | 24.7 (24.0–25.5) |
| 36 | 4.7 (0.0–10.5) | 19.2 (7.6–30.8) | 22.9 (22.2–23.6) | 20.0 (19.4–20.7) |
| 37 | 12.3 (2.4–22.3) | 21.7 (8.5–35.0) | 18.0 (17.3–18.6) | 14.1 (13.5–14.6) |
| 38 | 13.7 (1.5–26.0) | 23.1 (7.2–38.9) | 11.8 (11.3–12.3) | 13.1 (12.5–13.6) |
| 39 | 18.3 (0.5–36.2) | 33.6 (9.5–57.8) | 9.8 (9.3–10.3) | 14.6 (13.9–15.3) |
| 40 | 22.5 (0.0–50.2) | 25.18 (0.0–54.51) | 10.4 (9.8–11.0) | 5.83 (5.25–6.40) |
a Composite risk is the risk of stillbirth at this gestational age (weeks) plus the risk of infant death following delivery at the subsequent gestational age (weeks).
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