Results:
We analyzed 1,168,378 pregnancies in the UPDB and identified 32,823
cases (2.8%) of PA over the years 1939 – 2020 after excluding for
missing data or ineligible pedigrees. Relatives included in the primary
analysis were 313,823 FDRs, 559,116 SDRs, and 1,242,936 TDRs (Fig. 1).
16,542 (50.4%) of these cases were identified by the term “antepartum
bleeding” without a known diagnosis of placenta previa. The majority of
cases were identified based on birth certificate data (83.7%), with the
remaining cases identified from medical records (13.4%), fetal death
certificates (2.3%) and maternal death certificates (0.5%).
Individuals affected by PA were more likely to smoke (8.6% vs. 6.4%,p -value <0.001), use drugs (1.2% vs. 0.5%,p -value <0.001), have pre-gestational diabetes (0.4%
vs. 0.3%, p -value <0.001), hypertension (7.5% vs.
5.6%, p -value <0.001), or a uterine anomaly (0.2% vs.
0.1%, p -value <0.001), experience PROM (4.3% vs.
1.3%, p -value <0.001), have less than a high school
education (8.7% vs. 6.1%, p -value <0.001) and were
more likely to be Hispanic (9.5% vs. 8.2%, p -value
<0.001) and less likely to be White (95.1% vs. 96.0%,p -value <0.001). See Table 1 for full details.
Table 2 represents results from the primary PA familial risk analysis.
PA appears to be heritable, with a statistically significant risk
transmitted to FDRs and SDRs. FDRs inherit an increased odds of PA with
an aOR 1.18 (95% CI: 1.12 – 1.23, p <0.001). SDRs
also inherit an increased odds of PA with an aOR 1.09 (95% CI: 1.06 –
1.13, p <0.001). TDRs do not appear to inherit a
significant PA risk with an aOR 1.01 (95% CI: 0.99 – 1.03,p =0.428). When stratified by number of pregnancies affected by
PA, FDRs of cases with two or more PAs inherit a more significant odds
of PA with aOR 1.38 (95% CI: 1.17 – 1.63, p <0.001).
The measures of association are also higher for SDRs and TDRs when their
family member was affected by two or more PAs, with the estimation for
SDRs nearing statistical significance (Fig. 2). Through a sensitivity
analysis in which cases of PA obtained by the code “antepartum
bleeding” were removed, the risk inherited by FDRs increased to an aOR
1.20 (95% CI: 1.12 – 1.27, p <0.001), while the risk
for SDRs was similar at an aOR 1.09 (95% CI: 1.05 – 1.14, p<0.001). The association for TDRs did not reach statistical
significance (Table 3). All relative-driven familial risk analyses were
adjusted for by available demographic variables for relatives: age, year
of pregnancy, race, ethnicity, education level, and parity.
For the ego-driven subgroup analysis, we analyzed 1,168,378 pregnancies
in the UPDB and identified 53,072 cases (4.5%) of PA matched to 159,124
controls over the years 1939 – 2020 after excluding for missing data
(Fig. S1). The majority of cases were identified based on birth
certificate data (82.2%), with the remaining cases identified from
medical records (14.9%), fetal death certificates (2.5%) and maternal
death certificates (0.4%). Demographic differences between cases and
controls were similar to the relative-driven method. See Table S1 for
full details. Table 4 depicts clinical risk factors with estimated
adjusted odds ratios associated with PA. Of these, PROM was most highly
associated with PA with an OR 2.18 (95% CI: 1.80 – 2.64, p<0.001). The presence of a uterine anomaly was also highly
associated with PA with an OR 2.17 (95% CI: 1.18 – 3.97,p =0.004).
Table 5 represents the results of the ego-driven familial risk analysis
adjusting for demographic and potentially confounding clinical
variables. If an individual has a first-degree family history of PA,
their odds of developing PA is estimated at an aOR 1.16 (95% CI: 1.03
– 1.31, p =0.014). Using this alternative method of analysis, the
odds estimated for an individual with second- and third-degree relatives
affected by PA is not statistically significant.