Increased risk of stillbirth, ectopic pregnancy linked with primary C-sections

Key clinical point: Primary cesarean section may be linked to a slightly increased risk of stillbirth and ectopic pregnancy.

Major finding: A primary cesarean section increased the risk of stillbirth (hazard ratio 1.14) and ectopic pregnancy (HR 1.09) but not miscarriage, compared with women with a spontaneous vaginal delivery for their first birth.

Data source: A population-based cohort study with Danish national registry data on 832,996 primiparous women with a live birth between Jan. 1, 1982, and Dec. 31, 2010.

Disclosures: The research was supported by the National Perinatal Epidemiology Centre in Cork, Ireland, and as part of the Health Research Board PhD Scholars program in Health Services Research. Dr. Louise C. Kenny is a Science Foundation Ireland Principal Investigator and director of Centre, INFANT, funded by Science Foundation Ireland.

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Study findings are unsurprising, with uncertain clinical relevance

Despite the increase in the

number of cesarean deliveries around the world over the past decades, there is

not a clinically significant increase in attendant maternal-fetal

complications. Thus, although the Danish study findings are neither novel nor

surprising, ultimately this study supports the observation that cesarean

delivery is another safe route for both the mother and child. It also is crucial

to recognize that this study is not a strict comparison of whether vaginal

delivery is safer than cesarean delivery, but an examination of how C-sections

may be linked to subsequent pregnancy complications.

The data for ectopic pregnancies presented in this

study have only marginal statistical relevance, but not a great clinical

significance. Additionally, a woman’s prior gynecologic history, such as

infections or surgical scarring due to the C-section procedure, greatly

influences the risk for ectopic pregnancy. Because many ectopic pregnancies can

abort prior to the detection of pregnancy, drawing any major conclusions from

these results is quite difficult.

It also is unclear to what extent the incomplete data

could influence how we interpret the findings of this study. As the fields of

developmental biology, teratology, biochemistry, and reproductive immunology

have advanced, so too has our understanding of the complex mechanisms involved

in successful pregnancy outcomes. Basing clinical applications on the findings from

this study, where gaps exist in the investigators’ knowledge of the women’s

overall health, becomes much more nebulous, and any conclusions should be

cautiously made and not extrapolated too much.

Dr. E. Albert Reece, Ph.D., MBA, is vice president for medical affairs at the University of Maryland, Baltimore, the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. He made these comments in an interview.



Both elective and emergency cesarean sections in first births appear to slightly increase the risk of stillbirth and ectopic pregnancy in subsequent pregnancies, according to a new study.

Compared with women whose first birth was a spontaneous vaginal delivery, primiparous women with a primary C-section were 14% more likely to have a subsequent stillbirth and 9% more likely to have a later ectopic pregnancy, but were no more likely to have a subsequent miscarriage, reported Sinéad O’Neill of Cork University Maternity Hospital, Ireland, and her associates (PLoS Med. 2014 July 1 [doi:10.1371/journal.pmed.1001670]).

The analysis was limited by incomplete data, and the increased rate of stillbirths and/or ectopic pregnancies could be driven by underlying factors that contributed to the need for a C-section, the researchers noted.

They analyzed Danish national registry data on 832,996 primiparous women with a live birth between Jan. 1, 1982, and Dec. 31, 2010, followed until the next stillbirth, miscarriage, ectopic pregnancy, live birth, death or emigration. Miscarriage was defined as loss before 28 weeks’ gestation until April 2004, and before 22 weeks’ gestation from 2004 onward.

The fully-adjusted analysis controlled for the following:

• Maternal age, origin, and marital status.

• Previous stillbirth, miscarriage, or ectopic pregnancy.

• Birth year.

• Socioeconomic status (mother’s education and both parents’ gross income).

• Medical complications in the first live birth, including multiples, diabetes, gestational diabetes, placental abruption, placenta previa, and hypertensive disorders.

• Gestational age at birth and birth weight.

The researchers lacked data on maternal body mass index, smoking status, and fertility treatment, as well as causes of stillbirth, maternally requested C-sections, and the gestational ages of the stillbirths and miscarriages.

The increased rate of stillbirth (hazard ratio 1.14) among women with a primary C-section, compared with women with an initial spontaneous vaginal birth, translated to an absolute risk increase of 0.03% and a number needed to harm of 3,333. Emergency C-sections showed a barely higher risk (HR 1.15), but the risk with elective C-sections (HR 1.11) did not reach statistical significance (95% CI 0.91, 1.35).

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