Objective
The objective of the study was to evaluate the ongoing risk of intrauterine fetal demise (IUFD) in nonanomalous pregnancies affected by polyhydramnios.
Study Design
We analyzed a retrospective cohort of all singleton, nonanomalous births in California between 2005 and 2008 as recorded in a statewide birth certificate registry. We included all births between 24+0 and 41+6 weeks’ gestational age, excluding multiple gestations, major congenital anomalies, and pregnancies affected by oligohydramnios. Polyhydramnios was identified by International Classification of Diseases , ninth revision, codes. χ 2 tests were used to compare the dichotomous outcomes, and multivariable logistic regression analyses were then performed to control for potential confounders. We analyzed the data for pregnancies affected and unaffected by polyhydramnios. The IUFD risk was expressed as a rate per 10,000.
Results
The risk of IUFD in pregnancies affected by polyhydramnios was greater at every gestational age compared with unaffected pregnancies. The IUFD risk in pregnancies affected by polyhydramnios was more than 7 times higher than unaffected pregnancies at 37 weeks at a rate of 18.0 (95% confidence interval [CI], 9.0–32.6) vs 2.4 (95% CI, 2.0–2.5) and was 11-fold higher by 40 weeks’ gestational age at a rate of 66.3 (95% CI, 10.8–68.6) vs 6.0 (95% CI, 5.1–6.3) in unaffected pregnancies. When adjusted for multiple confounding variables, the presence of polyhydramnios remained associated with an increased odds of IUFD in nonanomalous singleton pregnancies, with an adjusted odds ratio of 5.5 (95% CI, 4.1–7.6).
Conclusion
Ongoing risk of IUFD is greater in low-risk pregnancies affected by polyhydramnios at all gestational ages compared with unaffected pregnancies with the greatest increase in risk at term. Although further study is needed to explore the underlying etiology of polyhydramnios in these cases, the identification of polyhydramnios alone may warrant increased antenatal surveillance.
Amniotic fluid volume supports normal fetal growth and development and protects the fetus from trauma. Initially increasing from 10 to 30 weeks of gestation, the volume of amniotic fluid then slows or remains unchanged until 36–38 weeks and then it gradually decreases.
Polyhydramnios is excess amniotic fluid in pregnancy and is generally defined as a deepest vertical pocket measuring greater than 8 cm or a 4-quadrant amniotic fluid index greater than 25 cm. Polyhydramnios affects 1–2% of pregnancies and has been associated with a wide variety of high-risk maternal and fetal conditions and adverse pregnancy outcomes. In many cases, an adverse outcome can be related to the underlying maternal or fetal etiology for polyhydramnios; however, the risk of adverse outcome remains elevated, even in the greater than 50% of cases in which polyhydramnios remains unexplained.
Attempts have been made to assess the risk of perinatal death in pregnancies affected by polyhydramnios. For example, it was reported that women with pregnancies with persistent polyhydramnios experienced a significant increase in perinatal mortality including a relative risk of 7.7 for fetal death in pregnancies with persistent polyhydramnios compared with pregnancies with resolved polyhydramnios, including both anomalous and nonanomalous pregnancies.
Since then, multiple attempts have been made to identify perinatal mortality in pregnancies affected by polyhydramnios without a known anomaly, with most studies finding that pregnancies affected by polyhydramnios are associated with an increase in perinatal mortality. This was supported by a metaanalysis from 2007, which showed a 2- to 5-fold increased risk of perinatal mortality. In spite of the known impact of gestational age on the risk of intrauterine fetal demise (IUFD) in pregnancies affected by other conditions, no studies have specifically demonstrated whether the increased risk of IUFD in pregnancies affected by polyhydramnios varies by gestational age.
In light of the risk of fetal death, heightened antenatal surveillance has been advised to assess fetal health and fluid dynamics in the setting of polyhydramnios. This recommendation was endorsed by the American College of Obstetricians and Gynecologists in 1999 and reaffirmed in 2009; however, a revised practice bulletin published in 2014 omitted polyhydramnios from the list of pregnancy-related conditions for which antenatal testing is recommended.
Given this background, the aim of the current study was to further characterize the risk of IUFD in singleton, nonanomalous pregnancies affected by idiopathic polyhydramnios by each week of gestation. Our hypothesis was that the risk would increase throughout the preterm and term periods.
Materials and Methods
To examine the risk of IUFD at a given week of gestation based on the presence or absence of polyhydramnios, we conducted a retrospective cohort study of all births between 24+0 and 41+6 weeks’ gestational age (GA) in California between 2005 and 2008 as recorded in a statewide birth certificate registry that is linked with hospital discharge data and death certificate data. Polyhydramnios was identified by International Classification of Diseases , ninth revision codes (657, 657.0, 657.00, 657.01, 657.03).
IUFD was defined as intrauterine fetal death occurring after 20 weeks’ GA and before the time of delivery. We excluded all multiple gestations, pregnancies affected by oligohydramnios, and major congenital anomalies based on the International Classification of Diseases , ninth revision, codes 740–759 . χ 2 tests were used to compare dichotomous outcomes. Statistical significance was indicated by a probability value of P < .05. Multivariable logistic regression analyses were then performed to control for potential confounding variables including race/ethnicity, maternal age, college education, fewer than 5 prenatal visits, insurance status, parity, gestational age at delivery, chronic and gestational diabetes mellitus, and chronic hypertension. The results were reported as adjusted odds ratios with 95% confidence intervals (CIs).
The risk of IUFD encountered at each GA was calculated using a pregnancies at-risk life table method, which accounts for all ongoing pregnancies in the denominator and uses the half-week correction described by Smith. This calculation includes the number of IUFDs during a given GA week in the numerator divided by the total number of ongoing pregnancies minus half of the deliveries that occurred during the GA week in question, accounting for the fact that IUFDs are evenly distributed throughout the week of gestation.
We analyzed data for pregnancies affected and unaffected by polyhydramnios. The IUFD risk was expressed as a rate per 10,000. A moving average algorithm was applied to our graphs using simple 3 point smoothing to even short-term fluctuations in the data and highlight the overall trends. This study was approved by the Institutional Review Board at Oregon Health and Science University (IRB00009487, approved March 13, 2013) and of the State of California.
Results
We identified 1,850,951 pregnancies meeting inclusion criteria of which 6768 (0.4%) were affected by polyhydramnios. Maternal race/ethnicity, educational status, advanced maternal age or maternal age younger than 21 years at delivery, parity, and fetal sex were significantly different between the 2 groups ( Table 1 ). Additionally, women with chronic hypertension and pregestational or gestational diabetes mellitus were more common in pregnancies affected by polyhydramnios ( P < .001). There was no difference in documented insurance status or fewer numbers of prenatal care visits.
| Demographic | No polyhydramnios, % | Polyhydramnios, % | P value a |
|---|---|---|---|
| Race/ethnicity | < .001 | ||
| White (non-Hispanic) | 26.8 | 34.2 | |
| Black (non-Hispanic) | 5.10 | 5.80 | |
| Hispanic | 54.6 | 49.7 | |
| Asian/Pacific Islander | 11.6 | 8.50 | |
| Other | 1.90 | 1.80 | |
| Maternal age ≥35 y | 16.8 | 26.2 | < .001 |
| Maternal age ≤20 y | 9.60 | 5.80 | < .001 |
| Some college | 44.3 | 45.5 | .04 |
| <5 prenatal care visits | 4.20 | 4.50 | .31 |
| Public insurance | 48.6 | 49.1 | .44 |
| Nulliparous | 39.1 | 33.0 | < .001 |
| Male fetal sex | 51.0 | 55.1 | < .001 |
| Chronic hypertension | 1.00 | 2.60 | < .001 |
| Pregestational diabetes | 0.70 | 4.20 | < .001 |
| Gestational diabetes | 6.20 | 18.40 | < .001 |
Multivariable logistic regression analysis was then performed to control for potential confounding variables ( Table 2 ). We found that polyhydramnios was associated with an increased risk for IUFD in nonanomalous singleton pregnancies, with an adjusted odds ratio of 5.5 (95% CI, 4.1–7.6). In an additional analysis of pregnancies excluding gestational and pregestational diabetes, the adjusted odds ratio for polyhydramnios associated with IUFD was 6.2 (95% CI, 4.2–8.9).
| Variable | Adjusted odds ratio (95% CI) |
|---|---|
| Polyhydramnios | 5.5 (4.1–7.6) |
| Race/ethnicity | |
| Black (non-Hispanic) | 1.6 (1.3–1.9) |
| Hispanic | 1.2 (1.0–1.3) |
| Asian/Pacific Islander | 0.8 (0.7–1.0) |
| Maternal age ≥35 y | 2.2 (1.9–2.4) |
| Maternal age ≤20 y | 0.2 (0.1–0.3) |
| Some college | 0.7 (0.6–0.8) |
| Male fetus | 1.0 (0.9–1.1) |
| <5 prenatal care visits | 3.5 (3.0–4.1) |
| Public insurance | 1.3 (1.2–1.5) |
| Nulliparous | 1.7 (1.5–1.9) |
| Chronic hypertension | 0.9 (0.6–1.3) |
| Pregestational diabetes | 3.7 (2.9–4.8) |
| Gestational diabetes | 1.0 (0.8–1.2) |
When stratifying the risk of IUFD by gestational age, the risk in pregnancies affected by polyhydramnios was greater at every gestational age compared with unaffected pregnancies. The lowest rate of IUFD was seen at 25–26 weeks for affected pregnancies and then rose throughout gestation. Unaffected pregnancies demonstrated a relatively stable rate of IUFD per ongoing pregnancy with a nadir in the early third trimester (27–30 weeks).
At term, the rate of IUFD increased in both groups; however, the rate of increase was greater in pregnancies affected by polyhydramnios. By 37 weeks, the risk of IUFD in affected pregnancies was 7 times higher than unaffected pregnancies (18.0; 95% CI, 9.0-32.6 vs 2.4; 95% CI, 2.0-2.5) and was 11-fold higher by 40 weeks’ GA (66.3; 95% CI, 10.8-68.6 vs 6.0; 95% CI, 5.1–6.3) ( Table 3 ).
| Polyhydramnios | Unaffected pregnancies | ||||||
|---|---|---|---|---|---|---|---|
| GA | Ongoing pregnancies, n | IUFDs, n | IUFD per 10,000 ongoing pregnancy (95% CI) | GA | Ongoing pregnancies, n | IUFD, n | IUFD per 10,000 ongoing pregnancy (95% CI) |
| 25 | 6754 | 3 | 4.4 (–0.6 to 9.5) | 25 | 1,842,953 | 262 | 1.4 (1.2–1.6) |
| 26 | 6746 | 2 | 4.8 (–1.1 to 7.1) | 26 | 1,841,690 | 256 | 1.4 (1.2–1.6) |
| 27 | 6738 | 6 | 7.8 (1.8–16.0) | 27 | 1,840,249 | 237 | 1.3 (1.1–1.5) |
| 28 | 6718 | 7 | 10.8 (2.7–18.2) | 28 | 1,838,659 | 235 | 1.3 (1.1–1.4) |
| 29 | 6698 | 9 | 12.3 (4.7–22.2) | 29 | 1,836,688 | 251 | 1.3 (1.2–1.5) |
| 30 | 6676 | 8 | 12.8 (3.7–20.3) | 30 | 1,834,104 | 234 | 1.3 (1.1–1.4) |
| 31 | 6644 | 9 | 12.8 (4.7–22.5) | 31 | 1,830,447 | 243 | 1.3 (1.2–1.5) |
| 32 | 6597 | 8 | 11.4 (3.8–20.6) | 32 | 1,825,399 | 247 | 1.4 (1.2–1.5) |
| 33 | 6533 | 5 | 10.4 (1.0–14.4) | 33 | 1,817,771 | 261 | 1.5 (1.3–1.6) |
| 34 | 6452 | 9 | 13.4 (4.9–23.2) | 34 | 1,805,208 | 294 | 1.6 (1.5–1.8) |
| 35 | 6330 | 11 | 15.8 (7.3–28.0) | 35 | 1,782,747 | 321 | 1.8 (1.6–2.0) |
| 36 | 6111 | 8 | 16.4 (4.3–22.8) | 36 | 1,744,916 | 349 | 2.0 (1.8–2.3) |
| 37 | 5693 | 11 | 18.0 (9.0–32.6) | 37 | 1,674,738 | 361 | 2.4 (2.0–2.5) |
| 38 | 4892 | 7 | 21.1 (5.2–28.1) | 38 | 1,515,361 | 427 | 3.2 (2.9–3.5) |
| 39 | 3502 | 8 | 29.1 (12.0–48.2) | 39 | 1,158,908 | 364 | 4.2 (3.9–4.4) |
| 40 | 1815 | 5 | 66.3 (10.8–68.6) | 40 | 651,985 | 256 | 6.0 (5.1–6.3) |
| 41 | 703 | 7 | 113.1 (64.1–247.0) | 41 | 244,197 | 128 | 11.3 (7.3–9.6) |
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