Maternal and neonatal outcomes following abnormally invasive placenta: a population-based record linkage study HEATHER J. BALDWIN1,2, JILLIAN A. PATTERSON1,3 , TANYA A. NIPPITA1,3,4 , SIRANDA TORVALDSEN1,3,5, IBINABO IBIEBELE1,3, JUDY M. SIMPSON6 & JANE B. FORD1,3 1Clinical and Population Perinatal Health Research, Kolling Institute, Northern Sydney Local Health District, St Leonards, New South Wales, 2Biostatistics Training Program, New South Wales Ministry of Health, North Sydney, New South Wales, 3Sydney Medical School Northern, University of Sydney, Sydney, New South Wales, 4Department of Obstetrics and Gynaecology, Royal North Shore Hospital, St Leonards, New South Wales, 5School of Public Health and Community Medicine, University of New South Wales, Kensington, New South Wales, and 6Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia ACTA Obstetricia et Gynecologica Scandinavica Journal Club -Obstetrics- November 2017 Edited by Francesco D’Antonio

Introduction Abnormally invasive placenta (AIP) encompasses a spectrum of conditions characterized by the invasion of the trophoblastic tissue trough the myometrium and uterine serosa. According to the severity of invasion, three different types of AIP have been described: placenta accreta, increta and percreta. Incidence estimates of AIP vary widely, ranging from 1.7 to 90 per 10 000 (1,2). This wide range is likely due to differences in diagnosis and case definition (histopathological or clinical) of AIP. The main risk factors for AIP are placenta previa and prior cesarean section. AIP is associated with severe pregnancy complications such as postpartum hemorrhage and requires complex multidisciplinary management which may include large-volume blood transfusion, embolization of major arteries, hysterectomy, and admission to intensive care. Prenatal diagnosis of AIP is fundamental as it has been shown to reduce the burden of maternal and fetal complications associated with these anomalies.

To investigate maternal and neonatal outcomes in women affected by AIP Aim of the study To investigate maternal and neonatal outcomes in women affected by AIP

Material and Methods Study design: Population-based record linkage study, including all women who gave birth in New South Wales, Australia, between 2003 and 2012. Inclusion criteria: Women affected compared to those not affected by AIP. Maternal and neonatal characteristics, pregnancy, labor and birth data were obtained from the NSW Perinatal Data Collection, which records all births of at least 400 g birthweight or 20 weeks’ gestation. Data on outcomes, risk factors and other covariates were obtained from the NSW Admitted Patient Data Collection (a census of all hospital admissions in New South Wales, with diagnoses and procedures coded using the International Classification of Diseases) from January 2002 to December 2012. Main outcome measures: Composite measures of severe maternal and neonatal morbidity. Maternal outcomes: Obstetric hemorrhage, need for blood transfusion, embolization in the birth admission, hysterectomy within six months, manual removal of placenta within six weeks, readmission within six weeks, and intensive care unit (ICU) admission. Neonatal outcomes: Gestational age at birth, small-for-gestational-age newborn, Apgar score at five minutes, resuscitation, and admission to neonatal intensive care unit (NICU) or special care nursery, stillbirth, neonatal death and death prior to discharge, length of in hospital stay.

Material and Methods Statistical analysis: Modified Poisson regression models with robust error variances were used, taking into account clustering within individual mothers (all models, to allow for repeat pregnancies) and deliveries. Potential confounders were included in the full multivariable model where p < 0.2 in univariate analysis. Backwards selection was used to remove factors not significant at the 1% level from the final model. Results are presented as relative risks (RR) with 99% confidence intervals (CI). Adjusted and crude analyses were repeated with stratification by gestational age (term and preterm).

Results There were 922925 deliveries of infants of at least 20 weeks’ gestation during the period 2003 to 2012. 2285 deliveries involved an abnormally invasive placenta diagnosis, involving a total of 2248 mothers. The overall rate of AIP throughout the study period was 24.8 per 10 000. The annual rate of AIP increased by30.6% over the study period, from 20.6 per 10 000 to26.9 per 10 000 (p = 0.009) For primiparous mothers the rate was 22.7 per 10 000, with a non-significant increase from 20.8 per 10 000 in 2003 to 22.5 in 2012 (p = 0.29).

Results Mothers with AIP were older, had higher parity and greater socioeconomic advantages. A higher proportion of mothers with AIP had placenta previa, a history of cesarean section, assisted reproductive technology in the year prior to birth, hypertension, and female infants compared to those without. Almost 40% of mothers with AIP had a cesarean delivery, compared with 29% for mothers without AIP . There were 70 multiple births to women with AIP (3.1%) compared with 13 887 (1.5%) for women without AIP. The median length of stay for the birth admission for mothers with AIP was five days [interquartile range (IQR) 4–7], compared with four (IQR 2–5) for those without. The median length of stay in the birth admission for infants born to a mother with AIP was four days (IQR 3–6) and three (IQR 2–5) for those without.

Results AIP was associated with poor maternal outcomes, including maternal morbidity, hemorrhage, maternal ICU admission and readmission. 12.3% with AIP underwent a hysterectomy within six months compared to 0.05% without AIP. No mothers with AIP died during the postnatal period Almost 25% of infants born to mothers with AIP were born preterm, compared with 7.3% among mothers without AIP. Both preterm and term infants born following AIP were at increased risk of neonatal morbidity and resuscitation. 3.3% of infants of mothers with AIP were stillborn compared with 0.6% for mothers without (RR 5.4, 99% CI 4.0–7.3) although the difference in risk was not significant when stratified by prematurity. The majority (92.2%) of stillbirths with AIP occurred at 32 weeks’ gestation or earlier, compared with 64.9% without AIP; 5.2% occurred at 33–36 weeks (without AIP: 13.0%); and only 2.6% at 37 weeks or later (without AIP: 22.1%).

Results AIP was associated with significantly higher maternal morbidity in the adjusted analysis [adjusted relative risk (aRR) 17.6, 99% CI 14.5–21.2]. AIP also increased the risk of neonatal morbidity, stillbirth or death more than threefold (aRR 3.1, 99% CI 2.7–3.5). Although there was no significant change in overall trends in place of birth among women with AIP (p = 0.08), the proportion of all deliveries with AIP in tertiary hospitals increased from 30.3% in 2003 to 36.1% in 2012 (without AIP: 26.7 to 28.7%, p < 0.001).

Limitations Retrospective analysis. Lack of stratification according to the severity of AIP. Information on hospital access to blood products was based on an audit conducted early in the study period and may not reflect availability at the end of the study period. Treatment of AIP has changed through the study period, which might have biased the figures for some of the adverse outcomes reported.

Conclusion AIP increases the risk of severe adverse outcomes for both mothers and babies. The severity of outcomes, combined with the increase in incidence, highlights the need for clinicians to be cognizant of the risks, particularly to infants. Physicians should maintain an index of suspicion of AIP, even among primiparae.