Pregnancy Loss and the Risk of Spontaneous Preterm Birth
Pregnancy Loss and the Risk of Spontaneous Preterm Birth
Study question: Do women with a previous miscarriage or termination of pregnancy have an increased risk of spontaneous preterm birth and is this related to previous cervical dilatation and curettage?
Summary answer: A single previous pregnancy loss (termination or miscarriage) managed by cervical dilatation and curettage is associated with a greater risk of SpPTB.
What is known already: Miscarriage affects ~20% of pregnancies and as many as a further 20% of pregnancies undergo termination.
Study design, size, duration: We utilized data from 5575 healthy nulliparous women with singleton pregnancies recruited to the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study performed between November 2004 and January 2011.
Participants/materials, setting, methods: The primary outcome was spontaneous preterm birth (defined as spontaneous preterm labour or preterm premature rupture of membranes (PPROM) resulting in preterm birth <37 weeks' gestation). Secondary outcomes included PPROM, small for gestational age, birthweight, pre-eclampsia and placental abruption.
Main results and the role of chance: Women with previous pregnancy loss (miscarriage or termination) were compared with those with no previous pregnancy loss. There were 4331 (78%) women who had no previous pregnancy loss, 974 (17.5%) who had one early previous pregnancy loss, 249 (4.5%) who had two and 21 (0.5%) who had three or four losses. Women with two to four previous losses, but not those with a single loss, had an increased risk of spontaneous preterm birth (adjusted OR 2.12; 95% CI 1.55, 2.90) and/or placental abruption (adjusted OR 2.30; 95% CI 1.36, 3.89) compared with those with no previous pregnancy. A single previous miscarriage or termination of pregnancy where the management involved cervical dilatation and curettage was associated with an increased risk of spontaneous preterm birth (adjusted OR 1.64; 95% CI 1.08, 2.50; 6% absolute risk and adjusted OR 1.83; 95% CI 1.35, 2.48; 7% absolute risk, respectively) compared with those with no previous pregnancy losses. This is in contrast with women with a single previous miscarriage or termination managed non-surgically who showed no increase risk (adjusted OR 0.86; 95% CI 0.38, 1.94; 3.4% absolute risk and adjusted OR 0.87; 95% CI 0.69, 1.12; 3.8% absolute risk, respectively).
Limitations, reasons for caution: Although every effort was made to record accurate previous pregnancy data, it was not feasible to confirm the history and management of previous pregnancy loss by hospital records. This may have introduced recall bias.
Wider implications of the findings: This large prospective cohort study of healthy nulliparous women has demonstrated that women with either a previous miscarriage or termination of pregnancy were at increased risk of spontaneous preterm birth if they were managed by procedures involving cervical dilatation and curettage. However, overall, women with a single pregnancy loss did not have an increased risk of having any other of the adverse pregnancy outcomes examined. In contrast, two to four previous pregnancy losses were associated with an increased risk of having a pregnancy complicated by spontaneous preterm birth and/or placental abruption. Research is required to determine whether non-surgical management of miscarriage or termination of pregnancy should be advocated over surgical treatment.
Study funding/competing interest(s) New Zealand: New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council; Evelyn Bond Fund, Auckland District Health Board Charitable Trust.
Australia: Premier's Science and Research Fund, South Australian Government.
Ireland: Health Research Board.
Leeds: Cerebra Charity, Carmarthen.
Manchester: National Health Service NEAT Grant; Manchester Biotechnology and Biological Sciences Research Council; University of Manchester Proof of Concept Funding.
King's College London: Guy's and St Thomas' Charity.
King's College London and Manchester: Tommy's—The Baby Charity.
Trial registration number: N/A.
Miscarriage affects ~20% of pregnancies (Regan and Rai, 2000), and in some regions including England and Wales as many as a further 20% of pregnancies undergo termination (Department of Health, 2011). Surgical evacuation of uterus with dilatation of the cervix is a common procedure for both spontaneous miscarriage (up to 80% of cases; Hemminki, 1998) and termination of pregnancy (~57–75%; Sedgh et al., 2007, 2012; Pazol et al., 2011).
Currently, women who have had one or two miscarriages or terminations of pregnancy are not considered high risk in subsequent pregnancies and consequently do not receive any altered or increased antenatal surveillance. The current data regarding adverse pregnancy outcomes following previous miscarriage are mixed and often conflicted (Schoenbaum et al., 1980; de Haas et al., 1991; Eskenazi et al., 1991; Ekwo et al., 1993; Basso et al., 1998; Buchmayer et al., 2004; Sheiner et al., 2005; Hammoud et al., 2007; Bhattacharya et al., 2008; van Oppenraaij et al., 2009).
Similar conflicting data exist regarding previous terminations of pregnancy and adverse pregnancy outcomes (Hogue et al., 1983; Pickering and Forbes, 1985; Atrash and Hogue, 1990; Lang et al., 1996; Zhou et al., 1999; Ancel et al., 2004; Moreau et al., 2005; Raatikainen et al., 2006; Smith et al., 2006). No difference in the risk of miscarriage, preterm delivery or small for gestational age (SGA) was observed in women with a previous termination of pregnancy managed by a medical technique or by vacuum aspiration, respectively, in one of the most recent large (11 814 participants) long-term safety studies on termination of pregnancy (Virk et al., 2007). However, the conflicting data possibly reflect differences in study design, lack of control for potential confounders (e.g. body mass index (BMI), smoking, substance abuse and low socio-economic status), inappropriately selected controls and/or a selection of heterogeneous populations including women of varying parities and co-existing medical conditions.
While there may be causative factors related to early pregnancy loss and complications in a subsequent pregnancy, the method of management of the pregnancy loss may also be influential. The traditional management of first trimester miscarriage or termination is cervical dilatation and curettage but in the absence of any strong evidence, women who have received surgical management are not generally informed of any potential risks in subsequent pregnancies nor do they usually receive altered antenatal care in subsequent pregnancies.
The aims of this study were 2-fold. First, we sought to clarify whether previous miscarriage or termination of pregnancy was associated with subsequent adverse pregnancy outcomes in a prospective cohort of nulliparous women. Secondly, we investigated whether any association was mediated by procedures involving cervical dilatation and curettage.
Abstract and Introduction
Abstract
Study question: Do women with a previous miscarriage or termination of pregnancy have an increased risk of spontaneous preterm birth and is this related to previous cervical dilatation and curettage?
Summary answer: A single previous pregnancy loss (termination or miscarriage) managed by cervical dilatation and curettage is associated with a greater risk of SpPTB.
What is known already: Miscarriage affects ~20% of pregnancies and as many as a further 20% of pregnancies undergo termination.
Study design, size, duration: We utilized data from 5575 healthy nulliparous women with singleton pregnancies recruited to the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study performed between November 2004 and January 2011.
Participants/materials, setting, methods: The primary outcome was spontaneous preterm birth (defined as spontaneous preterm labour or preterm premature rupture of membranes (PPROM) resulting in preterm birth <37 weeks' gestation). Secondary outcomes included PPROM, small for gestational age, birthweight, pre-eclampsia and placental abruption.
Main results and the role of chance: Women with previous pregnancy loss (miscarriage or termination) were compared with those with no previous pregnancy loss. There were 4331 (78%) women who had no previous pregnancy loss, 974 (17.5%) who had one early previous pregnancy loss, 249 (4.5%) who had two and 21 (0.5%) who had three or four losses. Women with two to four previous losses, but not those with a single loss, had an increased risk of spontaneous preterm birth (adjusted OR 2.12; 95% CI 1.55, 2.90) and/or placental abruption (adjusted OR 2.30; 95% CI 1.36, 3.89) compared with those with no previous pregnancy. A single previous miscarriage or termination of pregnancy where the management involved cervical dilatation and curettage was associated with an increased risk of spontaneous preterm birth (adjusted OR 1.64; 95% CI 1.08, 2.50; 6% absolute risk and adjusted OR 1.83; 95% CI 1.35, 2.48; 7% absolute risk, respectively) compared with those with no previous pregnancy losses. This is in contrast with women with a single previous miscarriage or termination managed non-surgically who showed no increase risk (adjusted OR 0.86; 95% CI 0.38, 1.94; 3.4% absolute risk and adjusted OR 0.87; 95% CI 0.69, 1.12; 3.8% absolute risk, respectively).
Limitations, reasons for caution: Although every effort was made to record accurate previous pregnancy data, it was not feasible to confirm the history and management of previous pregnancy loss by hospital records. This may have introduced recall bias.
Wider implications of the findings: This large prospective cohort study of healthy nulliparous women has demonstrated that women with either a previous miscarriage or termination of pregnancy were at increased risk of spontaneous preterm birth if they were managed by procedures involving cervical dilatation and curettage. However, overall, women with a single pregnancy loss did not have an increased risk of having any other of the adverse pregnancy outcomes examined. In contrast, two to four previous pregnancy losses were associated with an increased risk of having a pregnancy complicated by spontaneous preterm birth and/or placental abruption. Research is required to determine whether non-surgical management of miscarriage or termination of pregnancy should be advocated over surgical treatment.
Study funding/competing interest(s) New Zealand: New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council; Evelyn Bond Fund, Auckland District Health Board Charitable Trust.
Australia: Premier's Science and Research Fund, South Australian Government.
Ireland: Health Research Board.
Leeds: Cerebra Charity, Carmarthen.
Manchester: National Health Service NEAT Grant; Manchester Biotechnology and Biological Sciences Research Council; University of Manchester Proof of Concept Funding.
King's College London: Guy's and St Thomas' Charity.
King's College London and Manchester: Tommy's—The Baby Charity.
Trial registration number: N/A.
Introduction
Miscarriage affects ~20% of pregnancies (Regan and Rai, 2000), and in some regions including England and Wales as many as a further 20% of pregnancies undergo termination (Department of Health, 2011). Surgical evacuation of uterus with dilatation of the cervix is a common procedure for both spontaneous miscarriage (up to 80% of cases; Hemminki, 1998) and termination of pregnancy (~57–75%; Sedgh et al., 2007, 2012; Pazol et al., 2011).
Currently, women who have had one or two miscarriages or terminations of pregnancy are not considered high risk in subsequent pregnancies and consequently do not receive any altered or increased antenatal surveillance. The current data regarding adverse pregnancy outcomes following previous miscarriage are mixed and often conflicted (Schoenbaum et al., 1980; de Haas et al., 1991; Eskenazi et al., 1991; Ekwo et al., 1993; Basso et al., 1998; Buchmayer et al., 2004; Sheiner et al., 2005; Hammoud et al., 2007; Bhattacharya et al., 2008; van Oppenraaij et al., 2009).
Similar conflicting data exist regarding previous terminations of pregnancy and adverse pregnancy outcomes (Hogue et al., 1983; Pickering and Forbes, 1985; Atrash and Hogue, 1990; Lang et al., 1996; Zhou et al., 1999; Ancel et al., 2004; Moreau et al., 2005; Raatikainen et al., 2006; Smith et al., 2006). No difference in the risk of miscarriage, preterm delivery or small for gestational age (SGA) was observed in women with a previous termination of pregnancy managed by a medical technique or by vacuum aspiration, respectively, in one of the most recent large (11 814 participants) long-term safety studies on termination of pregnancy (Virk et al., 2007). However, the conflicting data possibly reflect differences in study design, lack of control for potential confounders (e.g. body mass index (BMI), smoking, substance abuse and low socio-economic status), inappropriately selected controls and/or a selection of heterogeneous populations including women of varying parities and co-existing medical conditions.
While there may be causative factors related to early pregnancy loss and complications in a subsequent pregnancy, the method of management of the pregnancy loss may also be influential. The traditional management of first trimester miscarriage or termination is cervical dilatation and curettage but in the absence of any strong evidence, women who have received surgical management are not generally informed of any potential risks in subsequent pregnancies nor do they usually receive altered antenatal care in subsequent pregnancies.
The aims of this study were 2-fold. First, we sought to clarify whether previous miscarriage or termination of pregnancy was associated with subsequent adverse pregnancy outcomes in a prospective cohort of nulliparous women. Secondly, we investigated whether any association was mediated by procedures involving cervical dilatation and curettage.