Archives of Gynecology and Obstetrics

, Volume 288, Issue 4, pp 939–944

Reproductive performance in the next pregnancy for nulliparous women with history of first trimester spontaneous abortion

Authors

    • Obstetrics and Gynecology Departments, Faculty of MedicineZagazig University
  • Soha Siam
    • Obstetrics and Gynecology Departments, Faculty of MedicineZagazig University
  • Mahmoud A. Seksaka
    • Obstetrics and Gynecology Departments, Faculty of MedicineZagazig University
  • Zakia M. Ibrahim
    • Obstetrics and Gynecology Departments, Faculty of MedicineSuezCanal University
Reproductive Medicine

DOI: 10.1007/s00404-013-2809-9

Cite this article as:
El Behery, M.M., Siam, S., Seksaka, M.A. et al. Arch Gynecol Obstet (2013) 288: 939. doi:10.1007/s00404-013-2809-9

Abstract

Objective

To determine whether interpregnancy interval after the first spontaneous abortion has an effect on reproductive performance of women in their next pregnancy.

Method

A prospective cohort study was conducted on 4,619 women with history of spontaneous abortion in their first pregnancy. Of them 2,422 (52.4 %) conceived within 6 months of the miscarriage (group A) and 2,197 47.6 % after 12 months (group B). The primary outcome was abortion, live birth, termination, or ectopic pregnancy in the next pregnancy. Secondary outcomes were preterm delivery, low birth weight infants, caesarean section rate and occurrence of preeclampsia, placental abruption and induced labour in the second pregnancy.

Results

Women who conceived again within 6 months were less likely to have another abortion, termination, or ectopic pregnancy compared with women with interpregnancy interval more than 12 months. Women with an interpregnancy interval more than 12 months were less likely to have live birth in the second pregnancy and more likely to have a caesarean section, preterm delivery, or infant of low birth weight compared with women who conceived again within 6 months.

Conclusions

Women who conceive within 6 months after their first spontaneous abortion have better reproductive outcomes and the lowest complication rates in their subsequent pregnancy.

Keywords

Interpregnancy intervalAbortionLive birthPregnancy outcome

Introduction

Miscarriage or spontaneous pregnancy loss before 24 completed weeks of gestation is estimated to affect 10–15 % of pregnancies [1]. While a spontaneous miscarriage is distressing at any time, it is particularly so if it occurs in the first pregnancy. Compared with women who have never been pregnant, those who have miscarried are more likely to experience threatened miscarriage, preterm birth, induced labour, and postpartum haemorrhage in the next pregnancy [2]. Previous work has focused on the risk of further miscarriage in these women [3], but there have been few attempts to study obstetric and perinatal outcomes in subsequent pregnancies after variable duration of interpregnancy intervals.

After abortion, the optimal timing of the next pregnancy is a frequently asked question. How long a couple should wait before trying for another pregnancy after abortion is controversial.

Some clinicians believe that there is little justification for delaying the next pregnancy [46] as an increased interpregnancy interval is unlikely to improve perinatal outcomes [7] whereas a new viable pregnancy and the birth of a child could enhance the women’s chances of recovery [4, 8]. Others suggest that women should be counseled about how to optimize their own health before and during pregnancy in preparation for subsequent conception.

An interpregnancy interval of less than 6 months after abortion was found to be independently associated with increased risks of adverse maternal and perinatal outcomes [9]. Therefore, current guidelines from the World Health Organization recommend that women should wait for at least 6 months before trying again [10]. Whereas others suggest a delay of up to 18 months, based on reports that interpregnancy intervals of 18–23 months after a live birth can enhance maternal and perinatal outcomes in the next pregnancy [1113]. However, any delay in attempting conception could further decrease the chances of conceiving especially in women over 35. Also women aged 40 have a 30 % chance of miscarriage, which rises to 50 % in those aged 45 or more with decreased chances of having a healthy baby [14, 15].

In this study, we attempted to address an important clinical question, which can assist clinicians in their counseling of women with miscarriage and can enable couples to make informed decisions about family planning. We aimed to determine the effect of interpregnancy interval duration after the first spontaneous abortion on reproductive performance of women in their next pregnancy.

Methods

In this prospective study, all nulliparous women attending antenatal care clinic of Zagazig University Hospitals, and Suez Canal University Hospitals between March 2009 to December 2012 with history of first trimester spontaneous abortion in the first recorded pregnancy were invited to participate. The study protocol runs in compliance with the Helsinki Declaration and approved by ethical committee of Zagazig University, and Suez Canal University Hospitals REF NO 2433,1979. All patients gave informed consent to participate in the study.

To determine the interpregnancy interval, we calculated the time interval between either the time of occurrence of previous abortion (based on a documented pregnancy that is confirmed by either early US or a positive urine or serum pregnancy test) or hospital admissions date in the previous abortion, and subtracted the number of gestation weeks of the second pregnancy at the time of the second admission. Gestational age in the second pregnancy was accurately assed by either a single sonogram before 10-week gestation or two sonogram with 4-week interval after 20-week gestation with adequate fetal growth parameters. We then divided the women into two groups depending on the time interval between the two pregnancies: less than 6 months (exposed group A) and more than 12 months (reference group B).

All patients included in the study should fulfill the following criteria: nullipara with history of previous one spontaneous abortion between 5–14 weeks of gestation, documented history of a previous pregnancy by either a positive serum or urine pregnancy test, beside US documention of gestational age before either home abortion event or hospital admission date, cases with unviable or missed abortion were included as well. All patients should have regular antenatal care follow-up visits in outpatient clinics of either Hospitals.

Women were excluded if gestational age in first pregnancy <5 weeks (before visible gestational sac) or >14 weeks (abortion occurred beyond first trimester), undocumented history of a previous pregnancy, the calculated interpregnancy interval (interval between two admissions minus the gestational age of second pregnancy) was less than four weeks. Women who had twin or multiple pregnancies as well as those who lack antenatal follow-up visits or delivery outside either hospitals were excluded as well.

The primary end point was reproductive outcome in the second pregnancy—namely, spontaneous and induced abortion, ectopic pregnancy, termination, stillbirth, and live birth. Confounding factors comprised maternal age at delivery, body mass index, type of abortion, mode of termination, whether the intervals between pregnancies were voluntary or not.

To assess the effects of interpregnancy interval on obstetric and perinatal complications, we carried out a subgroup analysis of women who had a second pregnancy continuing beyond 24 weeks and resulting in a live birth. Secondary outcomes in ongoing pregnancies were pre-eclampsia, placenta praevia, placental abruption, Postpartum haemorrhage, manual removal of placenta, instrumental delivery, preterm delivery, and low birth weight infants (<2,500 g). We defined preterm birth as occurring at <37 completed weeks of gestation. Adjustement for pregnancy specific variables like induction of labour, gestational age, and caesarean delivery was performed as appropriate.

Statistical analysis

SPSS version 17 was used for the statistical analysis. Results are presented as both crude and adjusted odds ratios with 95 % confidence intervals, using univariate and multivariate logistic regression (stepwise backward likelihood ratio method). In both the univariate and multivariate analyses, we considered a P value of less than 0.05 to be significant. We used the Hosmer and Lemeshow test to assess goodness of fit of the models and the likelihood ratio test to assess the relative contribution of terms entered into the model.

Power calculation showed that the study had 85 % power at the two sided 5 % significance level to detect a difference of 5 % or more in the occurrence of a second abortion, given that there were 2,422 women in the exposed (interpregnancy interval <6 months) and 2,197 women in the reference category more than 12 months.

Results

Data were available for a total of 4,697 women who had experienced abortion in their first pregnancy and had a subsequent pregnancy (2,694 cases from Zagazig University Hospitals, and 2,003 cases from Suez Canal University Hospitals). Seventy-eight women were excluded (52 lost follow-up, 2 had interpregnamcy interval <4 weeks, and 4 had twins pregnancy, 20 delivery outside both hospitals), thus 4,619 women formed the final study groups.

Of these 4,619 women, 2,422 (52.4 %) conceived within 6 months of the miscarriage (group A) and 2,197 (47.6 %) after 12 months (group B).

Compared with group B, women in group A were likely to be older [28.7 years (SD 5.4 years) vs. 26.2 (SD 4.2) years; P < 0.001]; Table 1

Threatened abortion rate was lower in group A than in group B [n = 51 (2.1 %) women vs. 81 (3.6 %) women], likewise induced and spontaneous abortion rate were both lower in group A than in group B [n = 63 (2.6 %) vs. 70 (3.1 %)] for the former and [n = 99 (4.08 %) vs. 117 (5.32 %)] for the later, respectively (Table 2). Incidence of ectopic pregnancy was higher in group B than in group A [39 (1.7 %) vs. 26 (0.07 %)], respectively; termination of pregnancy was also higher in group B than in Group A, (357 women 16.2 %) vs. (315 women, 13 %) p < 0.05 (Table 2). Live birth rates were highest in group A (n = 1,921 women, 79.31 %), and lowest (n = 1,574, 71.6 %) in group B (p < 0.01; Table 2). 
Table 1

Comparison of characteristics between women with different interpregnancy interval after the first miscarriage

Characteristicsa

Group A Interpregnancy interval <6 months

Group B Interpregnancy interval >12 months

P value

Age at second pregnancy event (years)

28.7 (4.9)

26.0 (5.2)

<0.001**

Body mass index (kg/m2)

24.20 (2.61)

24.11 (2.1)

0.11

Infertility treatment

225 (1.4 %)

336 (1.6 %)

0.83

Diabetes (type 1)

113 (0.7 %)

119 (0.74)

0.37

Chronic hypertension

157 (1.0 %)

245 (1.2 %)

0.52

** Statistically significant p values are presented in bold

aExpressed as mean (SD), median (IQR) or n (%)

Table 2

Second pregnancy outcome after the first spontaneous abortion in women with different interpregnancy interval duration

Second pregnancy outcome

Group A (n = 2,422) Interpregnancy interval <6 months

Group B (n = 2,197) Interpregnancy interval >12 months

Crude OR (99 % CI)

Adjusted OR (99 % CI)

Threatened abortion

51 (2.1)

81 (3.6)

2.2 (1.4–4.0)

3.3 (2.6–5.2)

Induced abortion

63 (2.6)

70 (3.1)

1.6 (0.9–3.6)

2.4 (1.4–4.3)

Spontaneous abortion

99 (4.08)

117 (5.32)

1.4 (0.7–2.3)

2.49 (1.0–3.9)

Termination

216 (9.91)

240 (10.92)

1.5 (0.6–2.6)

2.89 (1.4–4.3)

Ectopic pregnancy

26 (0.07)

39 (1.7)

1.3 (1.1–1.6)

1.3 (1.1–1.6)

Live birth

1,921 (79.31)

1,574 (71.6)

3.6 (2.4–5.3)

2.2 (1.8–4.7)

Still birth

23 (0.94)

40 (1.82)

1.4 (0.7–2.3)

2.49 (1.0–3.9)

Othera

23 (0.94)

36 (1.63)

1.4 (0.7–2.3)

2.49 (1.0–3.9)

aIncludes molar pregnancy and pregnancy of unknown location

After adjustment for maternal age at first pregnancy, adverse pregnancy outcomes in group A differed significantly from those in group B (Table 2). Women in group A were less likely to experience a threatened abortion (adjusted OR 3.3, 95 % CI 2.6-5.2), induced abortion (adjusted OR 2.4, 95 % CI (1.4-4.3), spontaneous abortion (adjusted OR 2.4, 95 % CI (1.0-3.9), termination of pregnancy (adjusted 2.89, 95 % CI (1.4-4.3), and ectopic pregnancy (adjusted OR 1.3, 95 % CI (1.1–1.6). Women in group A also have a higher live birth rate than those in group B (adjusted OR 2.2, 95 % CI (1.8–4.7). The highest risk of adverse outcomes was with women in group B who were more likely in their second pregnancy to have all previously mentioned complication in addition to still birth (adjusted OR 2.4, 95 % CI 1.0 to 3.9) (Table 2).

Table 3 shows risk of subsequent obstetric complication and interventions for women in their second pregnancy in both groups. Women in group A were less likely to have induced labour [308 (12.7 %) vs. 331 (15.0 %) adjusted OR 1.7], and elective caesarean section than those in (group B) [463 (19.1 %) vs. 477 (21.7 %) adjusted OR 2.2].
Table 3

Risk of subsequent obstetric complication and interventions in women with different interpregnancy interval duration

Complications

Group A Interpregnancy interval <6 months

Group B Interpregnancy interval >12 months

Crude OR (99 % CI)

Adjusted OR (99 % CI)

Pre-eclampsia

315 (13.00)

320 (14.5)

1.7 (1.4–3.0)

1.7 (1.5–3.2)

Placental abruption

208 (8.5)

196 (8.9)

1.5 (0.9–2.1)

 

Placenta praevia

176 (7.2)

181 (8.2)

1.0 (0.7–2.8)

 

Other antepartum haemorrhage

198 (8.1)

188 (8.5)

1.3 (1.1–1.6)

1.3 (1.1–1.6)

Induced labour

308 (12.7)

331 (15.0)

2.7 (2.2–3.2)

1.7 (1.5–1.8)

Elective caesarean section

463 (19.1)

477 (21.7)

2.2 (1.9–2.5)

2.2 (1.7–2.6)

Postpartum haemorrhage

123 (5.0)

119 (5.4)

5.9 (5.1–6.7)

5.9 (5.0–6.9)

Manual removal of placenta

76 (3.1)

69 (3.1)

0.5 (0.4–0.6)

0.5 (0.3–0.6)

Instrumental delivery

56 (2.4)

61 (2.7)

1.7 (1.3–2.3)

1.5 (1.1–2.1)

Values expressed as n (%)

No association was found between interpregnancy interval after abortion and pre-eclampsia, placenta praevia, or placental abruption in the second ongoing pregnancy (Table 3).

Table 4 shows perinatal complications by interpregnancy interval in women with live births in pregnancy after initial miscarriage. Values are numbers (percentages) of women. Preterm delivery (before 36 weeks) (adjusted OR 1.23, 95 % CI −1.02–1.48), or an infant of low birth weight (<2,500 g) (adjusted OR 1.21, 95 % CI −1.07–1.36) was more common in group B than in women in group A.
Table 4

Risk of subsequent perinatal complications in women with different interpregnancy interval duration

Complications

Group A Interpregnancy interval <6 months

Group B Interpregnancy interval >12 months

Crude OR (99 % CI)

Adjusted ORa (99 % CI)

Preterm delivery

139 (5.7)

162 (7.3 %)

1.8 (1.3–3.5)

2.8 (1.9–4.8)

Stillbirth

83 (3.4)

89 (4.0 %)

3.6 (2.0–6.5)

1.9 (1.1–3.6)

Neonatal deatha

21 (0.8 %)

34 (1.9)

5.1 (2.5–10.1)

2.3 (1.1–4.8)

Birthweight <2,500 gb

76 (3.1)

128 (5.8)

1.9 (1.6–2.4)

2.6 (1.3–3.7)

Apgar at 5 min, 7

48 (1.9)

97 (3.0)

1.1 (0.8–1.7)

 

aP < 0.5

bP < 0.001

Among the six factors studied using multivariate analyses, the only indepdent risk factor was whether the intervals between pregnancies were voluntary or not (Data not shown).

Discussion

The most published research has focused on interpregnancy intervals after live birth. Few have investigated interpregnancy intervals after abortion. This is most likely to be because of inaccurate or incomplete data on miscarriages, smaller numbers of women in this group. In addition, a retrospective history of the timing of miscarriage is likely to be unreliable.

One study reported perinatal outcomes after varying interpregnancy intervals and according to the type of pregnancy outcome that began the interval but data in this study were drawn from a demographic surveillance site in Bangladesh where induced abortion is illegal, possibly resulting in over-reporting of miscarriages [16]. Moreover, the reference group was women who had an initial live birth, thus potentially inflating the results.

Another study examined the effects of varying interpregnancy intervals after induced vs. spontaneous pregnancy termination on maternal and perinatal health. An interval of less than 6 months after abortion was independently associated with increased risks of adverse maternal and perinatal outcome [9]. However, in their study, they did not differentiate between induced and spontaneous abortion in the index pregnancy. Despite this limitation, the result of their study formed the basis for a WHO recommendation on birth spacing after abortion [10]. On the other hand, previous reports have suggested that adverse pregnancy outcomes are more likely to occur after miscarriage in women with increasing interpregnancy intervals [17, 18].

In this study, we have addressed an important clinical question: how much time has to be postponed by a couple to start a new pregnancy after a previous first trimester spontaneous abortion? Despite an extensive literature search, we were unable to detect any papers that had specifically looked at pregnancy outcomes following a single first recorded spontaneous abortion. Thus, to our knowledge, this is the first study of its kind. We designed a prospective study in which we compared several reproductive outcomes in two time frames before 6 months and after 12 months of the previous abortion finding that it is not necessary to delay for a new pregnancy in order to get a better reproductive prognosis. As a matter of fact, we found worst reproductive and perinatal performance in the group that get a subsequent pregnancy after 12 months. In this study, women who conceived within 6 months after their first spontaneous abortion had the lowest rates of second spontaneous or induced abortion, ectopic pregnancy, and termination in a subsequent pregnancy than those who conceived later. They were also least likely to deliver preterm or have an infant of low birth weight but were at highest risk of induced labour. Women with an interpregnancy interval of more than 12 months had the highest risks of ectopic pregnancy and termination and were most likely to have a caesarean section or preterm delivery and an infant of low birth weight.

Despite an extensive literature search, we were unable to detect any papers that had specifically looked at pregnancy outcomes following a single first recorded spontaneous abortion. Thus, to our knowledge, this is the first study of its kind. Our results run in agreement with one recent study that considered a large sample of women who delivered in Scottish hospitals and found that women who conceived within 6 months after a miscarriage had a better outcome of the subsequent pregnancy than women who waited longer to conceive again [19]. However, in their study they examined miscarriages that led to hospital contact only, therefore their results could not be generalized to all women with a miscarriage.

One possible explanation to our finding would be that women who become pregnant soon after an initial miscarriage may have been highly motivated such that their health-related behaviours may have favored more successful pregnancies as suggested previously [6]. In addition women who conceive again soon after their pregnancy loss may not have any depletion of vital nutrients because most abortions occur in the first trimester and are not associated with breast feeding. Thus, such women usually have a reduced risk of adverse pregnancy outcome because they are protected from maternal depletion hypothesis [16]. This hypothesis suggests that decreasing levels of folate in the mother after the fifth month of gestation onwards could remain low for an extended period of time after delivery resulting in folate insufficiency in women with short interpregnancy intervals. This could finally lead to neural tube defects, intrauterine growth restriction, and preterm birth. Additionally, breast feeding after a live birth leads to further depletion of folate in the mother compounding this effect [17].

It is unknown why a longer interval is associated with adverse outcomes such as miscarriage or ectopic pregnancy. One study offered two hypotheses. Firstly, a pregnancy may enhance the functional capacity of the reproductive system, which can wane over time, and with longer intervals the risks to a mother and baby may resemble those in a primigravida [11]. An alternative hypothesis is that factors associated with underlying subfertility, which can increase the time to the next pregnancy, could result in adverse perinatal outcomes [20, 21].

In this study, after adjustment for confounding clinical factors, we found that the only indepedant risk factor was whether the intervals between pregnancies were voluntary or not using multivariate analysis, meaning that factors associated with underlying subfertility is the most probable explanation leading to adverse pregnancy outcome in this group. In a systematic review, it was reported that women who conceived again within a short time after delivery tended to have a lower parity than those who waited longer [22]. A higher proportion of women with an interpregnancy interval of less than 6 months also did not have antenatal care; again, this could have influenced the outcomes reported in their review. Previous studies have reported that inadequate use of prenatal care is a more potent predictor of adverse pregnancy outcomes than interpregnancy interval [23, 24]. In this study, the potential confounding effects such as quality of, access to, and use of prenatal care were adequately estimated as all our patients had regular antenatal care visits till either delivery or a second hospital admission. Furthermore, we adjusted for other relevant confounding factors such as smoking (obstetric complications well recognized) and previous gynecological history (e.g., women with history of STI, PID, cervical surgery).

Interestingly, the results of this study, together with other recent article on the same topic (19), challenge the actual paradigm and clinical recommendation of the WHO. Points of strength of this study include its large sample size, prospective nature of the study, and that the potential for residual confounding factors was nullified as age-dependent risk of an adverse pregnancy outcome, body mass index, type of abortion, mode of termination, whether the intervals between pregnancies were voluntary or not.

We are aware that our study is not without drawbacks. First we only looked at IPI at less than 6 months and at more than 12 months, however women with IPI between 6–12 months were not included as well. Actually, we detect a relatively small number during our study period who conceived between 6 and 12 months, hence we choose only these two intervals. Another point to be mentioned is the retrospective nature of the miscarriage event which is based on the IPI recording of the mother’s memory of a previous miscarriage, and hence it was prone to recall bias.

We concluded that women who conceive within 6 months after their first spontaneous abortion have a better reproductive outcome and the lowest complication rates in their subsequent pregnancy than those who conceived after 12 months.

Conflict of interest

We declare that we have no conflict of interest.

Copyright information

© Springer-Verlag Berlin Heidelberg 2013