OBSTETRICS

Intrapartum Interventions for Singleton Pregnancies Arising From Assisted Reproductive Technologies Lu-Ming Sun, MD,1,2,3 Andrea Lanes, MSc,3,4 John C.P. Kingdom, MD,5 Huiling Cao, MSc,3 Michael Kramer, MD,6 Shi Wu Wen, PhD,3,4 Junqing Wu, PhD,7 Yue Chen, PhD,8 Mark C. Walker, MSc, MD3,4 School of Public Health, Fudan University, Shanghai, China

1

Fetal Medicine Unit, Division of Maternal-Fetal Medicine, Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Shanghai, China

2

OMNI Research Group, Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa ON

3

Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ottawa ON

4

Placenta Clinic, Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto ON

5

Department of Epidemiology, Biostatistics and Occupational Health and Department of Pediatrics, McGill University Faculty of Medicine, Montreal QC

6

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine, Ottawa General Hospital, University of Ottawa, Ottawa ON

7

Shanghai Institute of Planned Parenthood Research/WHO Collaborating Center on Human Research, Shanghai, China

8

Abstract Objective: To assess whether singleton pregnancies conceived by assisted reproductive technology (ART) are associated with an increased use of intrapartum interventions when compared with spontaneous singleton pregnancies. Methods: In total, 1327 ART pregnancies and 5222 spontaneous pregnancies during the period 2004 to 2008 were extracted from BORN (Better Outcomes Registry & Network) Ontario’s information system. The incidences of common intrapartum interventions were compared, and different classification systems for Caesarean section were used to compare the indications for these between singleton pregnancies following ART with or without intracytoplasmic sperm injection and singleton spontaneously conceived pregnancies. Results: Compared with spontaneous singleton pregnancies, the ART group had increased incidences of internal electronic fetal monitoring (OR 1.60; 95% CI 1.37 to 1.87), artificial rupture of membranes (OR 1.39; 95% CI 1.17 to 1.66), oxytocin

Key Words: Assisted reproductive technologies, intrapartum interventions, singleton pregnancies Competing Interests: None declared. Received on November 21, 2013 Accepted on April 10, 2014

augmentation of labour (OR 1.51; 95% CI 1.28 to 1.77), induction of labour (OR 1.31; 95% CI 1.14 to 1.50), and Caesarean section (OR 1.40; 95% CI 1.24 to 1.60). Conclusion: Singleton pregnancies resulting from ART were associated with more frequent use of several intrapartum interventions, including Caesarean section.

Résumé Objectif : Déterminer si les grossesses monofœtales attribuables aux techniques de procréation assistée (TPA) sont associées à une hausse du recours à des interventions intrapartum, par comparaison avec les grossesses monofœtales spontanées. Méthodes : Au total, 1 327 grossesses attribuables aux TPA et 5 222 grossesses spontanées s’étant déroulées au cours de la période 2004-2008 ont été extraites du système informatique BORN (Better Outcomes Registry & Network ou, en français, « bons résultats dès la naissance ») de l’Ontario. L’incidence des interventions intrapartum courantes a été comparée et divers systèmes de classification des césariennes ont été utilisés pour en comparer les indications dans le cadre des grossesses monofœtales attribuables aux TPA (avec ou sans injection intracytoplasmique d’un spermatozoïde) et dans le cadre des grossesses monofœtales spontanées. Résultats : Par comparaison avec le groupe « spontanée », le groupe « TPA » présentait une hausse de l’incidence du monitorage fœtal électronique interne (RC, 1,60; IC à 95 %,

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1,37 - 1,87), de la rupture artificielle des membranes (RC, 1,39; IC à 95 %, 1,17 - 1,66), de l’accélération du travail au moyen d’oxytocine (RC, 1,51; IC à 95 %, 1,28 - 1,77), du déclenchement du travail (RC, 1,31; IC à 95 %, 1,14 - 1,50) et de la césarienne (RC, 1,40; IC à 95 %, 1,24 - 1,60). Conclusion : Les grossesses monofœtales attribuables aux TPA ont été associées à une utilisation plus fréquente de plusieurs interventions intrapartum, dont la césarienne. J Obstet Gynaecol Can 2014;36(9):795–802

INTRODUCTION

A

ssisted reproductive technology has been increasingly used for subfertility problems since the first “testtube” baby was born in 1978.1 Worldwide, more than five million babies have been born with ART.1 The safety of ART in terms of its effect on maternal, fetal, and infant outcomes has been examined in a number of recent studies.2–5 Pregnancies achieved with ART, including singleton pregnancies, appear to have an increased risk of obstetric and perinatal complications,6 indicating a need for closer surveillance.7 However, there is a lack of evidence regarding the effect of intrapartum interventions used in pregnancies achieved with ART compared with those resulting from spontaneous conception. It is important that this issue be explored. Previous studies have estimated the risk of Caesarean section or induction of labour in ART pregnancies, but few have investigated the roles of other potentially confounding intrapartum interventions, such as fetal surveillance, pain relief, or augmentation of labour, owing to insufficient information in their data sets.6,8,9 Second, although pregnancies achieved with ART are at an increased risk of delivery by Caesarean section,4,9 previous studies have not been able to determine what some of the factors driving this risk were. It has been suggested that maternal request or physician preference may be contributing to the increased risk, although no data have been available to support this speculation.5 The objective of this study was to investigate whether singleton pregnancies resulting from ART are associated with an increased risk of intrapartum interventions because of adverse outcomes when compared with singleton pregnancies conceived spontaneously.

ABBREVIATIONS ARM

artificial rupture of membranes

ART

assisted reproductive technology

BORN

Better Outcomes Registry & Network

EFM

electronic fetal monitoring

796 l SEPTEMBER JOGC SEPTEMBRE 2014

METHODS

Data included in this study were extracted from BORN Ontario’s database, a web-based information system with manual data entry and uploads from electronic medical records. The database contained perinatal data on hospital births in Ontario from most hospitals and midwifery practice groups, representing between 85% and 98% of total births in Ontario for the period 2004 to 2008. Prenatal information includes maternal demographic characteristics, maternal health behaviours, pre-existing maternal health conditions, types of assisted reproductive technologies, pregnancy complications, intrapartum complications and interventions, and maternal and neonatal outcomes. The study included pregnant women who delivered a single live baby with a birth weight of 500g or greater or a gestational age of 20 weeks or greater during the period from March 1, 2004, to December 31, 2008. Excluded were women who had stillbirths (intrauterine fetal death occurring at ≥ 20 weeks) and women with pre-existing maternal health problems (chronic hypertension, type 1 and type 2 diabetes, heart disease, thyroid disease, systemic lupus erythematosus, alcohol dependence syndrome, asthma, HIV, hepatitis B, or psychiatric disorders). The ART group consisted of singleton pregnancies conceived through ART defined as vitro fertilization with or without intracytoplasmic sperm injection. For each ART case, four singleton pregnancies conceived spontaneously were matched by maternal age (within 2 years), parity (nulliparous and multiparous), and hospital level (small community, large community, or teaching hospital) at delivery and randomly selected. A total of 1327 eligible ART pregnancies and 5222 matched spontaneous pregnancies were identified in the BORN Ontario’s database for the study period. Between ART pregnancies and spontaneous pregnancies, we examined the differences in fetal surveillance during labour and delivery (external EFM, or internal EFM), augmentation of labour (artificial rupture of membranes, or use of oxytocin or prostaglandin, which was recorded only if labour type was spontaneous), pain relief (epidural analgesia), induction of labour, and Caesarean section. To explore the reasons for the differences in Caesarean section between the two study groups, we used the Robson classification system (Table 1), which classifies women in 10 categories according to parity, course of labour and delivery, gestation, previous record of pregnancy, presence of a uterine scar, and type of pregnancy (single or multiple); these categories are mutually exclusive, totally

Intrapartum Interventions for Singleton Pregnancies Arising From Assisted Reproductive Technologies

Table 1. Description of Robson classification system for women with Caesrean section10,11 1. Nulliparous women, single cephalic pregnancy, at greater than or equal to 37 weeks’ gestation, spontaneous labour 2. Nulliparous women, single cephalic pregnancy, at greater than or equal to 37 weeks’ gestation, either had labour induced or were delivered by Caesarean section before labour 3. Multiparous women, without a previous uterine scar, single cephalic pregnancy, at greater than or equal to 37 weeks, spontaneous labour 4. Multiparous women, without a previous uterine scar, single cephalic pregnancy at greater than or equal to 37 weeks’ gestation, either had labour induced or were delivered by Caesarean section 5. All multiparous women, with at least one previous uterine scar, single cephalic pregnancy, at greater than or equal to 37 weeks’ gestation 6. All nulliparous women, single breech pregnancy 7. All multiparous women, single breech pregnancy, including women with previous uterine scars 8. All women with multiple pregnancies, including women with previous uterine scars 9. All women with a single pregnancy with a transverse or oblique lie, including women with previous uterine scars 10. All women with a single cephalic pregnancy at less than 37 weeks’ gestation, including women with previous uterine scars

Table 2. Modified causal model with decision rules for major indication for Caesarean section with single and multiple diagnoses10 1. Cases having the diagnosis of maternal request were assigned to diagnostic “maternal request” (the diagnosis of maternal diagnosis was defined as Caesarean section required by mother without any medical indications) 2. Cases having the diagnosis of placenta previa were assigned to diagnostic “placenta previa” that had to be delivered by Caesarean section 3. All multiple-diagnosis deliveries in which one of the diagnoses was a previous Caesarean section were assigned to the diagnostic class “previous Caesarean section” 4. Cases having a diagnosis of breech presentation with either dystocia or fetal distress or both were assigned to the diagnostic class ‘breech.’ (This recognized breech presentation as a cause of both dystocia and fetal distress) 5. Cases having the diagnoses dystocia and fetal distress were assigned to the diagnostic “dystocia” (This recognized dystocia as a cause of fetal distress) 6. When none of the other five diagnoses appeared in the birth information, cases were assigned to the diagnostic class” fetal distress” 7. Cases that did not fall into one of the above four classes were classified as “other”

inclusive, prospective, and clinical relevant.10,11 In addition, the major indications for Caesarean section were further examined using a modified causal model that includes decision rules for assigning multiple indications to a single category (Table 2).10 We used chi-square tests to compare maternal and neonatal baseline characteristics between the two study groups. We then compared the frequencies of intrapartum interventions and the indications for Caesarean section using the Robson classification system and modified causal model. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression models. All analyses were performed using SAS software version 9.1 (SAS Inc., Cary, NC). The study was approved by the Ottawa Hospital Research Ethics Board.

RESULTS

Baseline maternal and neonatal characteristics of the two study groups are compared in Table 3. Mothers in the ART group were more likely to be non-smokers, to have initiated prenatal care in the first trimester, and to come from higher income neighbourhoods. Rates of preterm birth, low birth weight, and macrosomia were higher in the ART group than the spontaneous conception group. Intrapartum interventions in the two study groups are compared in Table 4. High rates of EFM, induction of labour, and Caesarean section were found in both groups. Rates of induction of labour, augmentation of labour with ARM, oxytocin, or both, and internal EFM were significantly higher in the ART group than in the spontaneous conception group. The rate of Caesarean section was 1.4 times higher in the ART group (42.6% vs. SEPTEMBER JOGC SEPTEMBRE 2014 l 797

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Table 3. Maternal and neonatal characteristics of the study population Characteristic*

ART group† n = 1327 n (%)

Non-exposed group n = 5222 n (%)

18 (1.36)

72 (1.38)

P

Maternal age, years < 25

0.97

25 to 29

141 (10.63)

564 (10.80)

30 to 34

482 (36.32)

1928 (36.92)

≥ 35

686 (51.70)

2658 (50.90)

No

1176 (95.69)

4475 (92.61)

Yes

53 (4.31)

357 (7.39)

Smoking during pregnancy

< 0.001

Initiating prenatal care in the first trimester

< 0.001

Yes

952 (90.93)

3235 (82.15)

No

95 (9.07)

703 (17.85)

Small community

116 (8.75)

464 (8.89)

Large community

832 (62.79)

3295 (63.16)

Teaching hospital

377 (28.45)

1458 (27.95)

Delivery hospital level

0.93

Parity

0.90

Nulliparous

938 (70.69)

3700 (70.85)

Multiparous

389 (29.13)

1522 (29.15)

< 20%

163 (12.84)

1105 (21.80)

20% to 40%

235 (18.85)

1033 (20.38)

40% to 60%

281 (22.14)

986 (19.46)

60% to 80%

290 (22.85)

978 (19.30)

> 80%

300 (23.64)

966 (19.06)

Yes

119 (9.00)

402 (7.74)

No

1203 (91.00)

4791 (92.26)

809 (97.82)

3486 (97.65)

18 (2.18)

84 (2.35)

Average neighbourhood income, quintile

< 0.001

Previous Caesarean section

0.13

Birth defects None At least one abnormality

0.76

Infant sex

0.36

Male

673 (50.72)

2721 (52.13)

Female

654 (49.28)

2499 (47.87)

28 (2.11)

53 (1.01)

Birth weight, g < 1500

< 0.001

1500 to 2499

77 (5.80)

226 (4.33)

2500 to 3999

1073 (80.86)

4397 (84.20)

149 (11.23)

546 (10.46)

< 37

144 (10.85)

345 (6.62)

≥ 37

1183 (89.15)

4863 (93.38)

≥ 4000 Gestational age at birth, weeks

< 0.001

*The following characteristics had missing values: smoking (488, 7.45%); initiating prenatal care in the first trimester (1564; 23.88%); birth defect (2152, 32.86%); and previous Caesarean section (34, 0.52%) †Exposed members matched 1:4 with non-exposed members; matching rate, 99.10%

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Table 4. Comparison of the use of intrapartum interventions between ART pregnancies and spontaneous pregnancies ART group n = 1327 n (%)

Non-exposed group n = 5222 n (%)

Adjusted OR (95% CI)†

Intrapartum EFM

1002 (77.55)

3865 (77.39)

1.00 (0.86 to 1.17)

External EFM

892 (69.04)

3652 (73.13)

0.81 (0.71 to 0.93)

Internal EFM

320 (24.77)

862 (17.26)

1.60 (1.37 to 1.87)

Intervention* Fetal monitoring

Augmentation ARM

242 (29.44)

877 (23.57)

1.39 (1.17 to 1.66)

Oxytocin

359 (43.67)

1267 (34.05)

1.51 (1.28 to 1.77)

ARM and oxytocin

472 (57.42)

1719 (46.20)

1.61 (1.37 to 1.89)

Prostaglandin

15 (1.82)

57 (1.53)

1.36 (0.75 to 2.46)

Epidural use

784 (59.67)

3037 (59.05)

1.04 (0.91 to 1.18)

Induction of labour

424 (32.10)

1404 (26.93)

1.31 (1.14 to 1.50)

Caesarean section

566 (42.65)

1786 (34.22)

1.40 (1.24 to 1.60)

In women who were induced

145 (34.20)

452 (32.22)

1.09 (0.85 to 1.39)

Before labour

254 (19.23)

686 (13.18)

1.50 (1.27 to 1.77)

During first stage of labour

168 (15.91)

529 (12.01)

1.31 (1.08 to 1.60)

67 (6.34)

215 (4.88)

1.38 (1.03 to 1.85)

During second stage of labour

*The following interventions had missing values: fetal monitoring (263, 4.02%); augmentation (2006, 30.63%); epidural use (92, 1.40%); induction of labour (14, 0.21%); Caesarean delivery (5, 0.08%); Caesarean delivery for women who are induced (1, 0.05%); before labour (17, 0.26%); during first or second stages of labour (1083, 16.55%) †OR and 95% CI adjusted for initiating time of prenatal care, smoking during the pregnancy, average neighbourhood income, gestational age at birth, and birth weight

34.2%; OR 1.4, 95% CI 1.2 to 1.6), and the increased risk of Caesarean section in the ART group was seen whether it was performed before labour, during the first stage of labour, or during the second stage of labour. However, no significant difference between the two groups was found in the rate of Caesarean section in women who had induction of labour (Table 4). Analysis according to the Robson classification showed that the risk of Caesarean section was significantly increased in women who conceived after ART in the following categories: 1. nulliparous, single cephalic presentation, ≥ 37 weeks, in spontaneous labour; 2. multiparous, single cephalic presentation, ≥ 37 weeks (excluding previous Caesarean section), in spontaneous labour; and 3. all single cephalic presentations, ≤ 36 weeks (including previous Caesarean section), but among no other categories (Table 5). Results of the modified causal model analysis showed that in women who conceived with ART, the odds of Caesarean section were significantly increased only in the maternal

request group and in women with placenta previa, but not in women with other indications for Caesarean section (Table 6). DISCUSSION

Singleton pregnancies conceived by ART were associated with an increase in rates of several intrapartum interventions, including internal EFM, ARM, and oxytocin for augmentation of labour, induction of labour, and Caesarean section. The higher incidence of Caesarean section in ART pregnancies, compared with pregnancies conceived spontaneously was observed at all stages of labour (before labour and during both the first and second stages of labour) but not in women who had labour induced, after adjusting for gestational age. Further analysis using the Robson system demonstrated that a significantly increased risk of Caesarean section was seen only in ART pregnancies delivered preterm and in term births after spontaneous labour at ≥ 37 weeks, but not for term births before labour. Analysis by major indications for Caesarean section indicated that the increased rate of Caesarean section in the ART group was partly attributable to placenta previa and maternal request. Increased maternal age has SEPTEMBER JOGC SEPTEMBRE 2014 l 799

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Table 5. Comparison of Caesarean section rate between the two study groups based on Robson criteria ART group n (%)

Non-exposed group n (%)

Adjusted OR (95%) CI

107 (25.91)

409 (20.77)

1.31 (1.02 to 1.69)

02.  Nulliparous, single cephalic, ≥ 37 weeks, 01.  induced or CS before labour

185 (51.25)

522 (44.62)

1.26 (0.98 to 1.62)

12 (9.76)

37 (5.35)

2.56 (1.24 to 5.28)

04.  Multiparous (excluding prev. CS), single cephalic, 01.  ≥ 37 weeks, induced or CS before labour

18 (20.69)

50 (17.79)

1.24 (0.65 to 2.36)

84 (89.36)

274 (86.98)

1.10 (0.51 to 2.36)

06.  All nulliparous breeches

55 (94.83)

201 (97.10)

0.44 (0.09 to 2.12)

07.  All multiparous breeches (including prev. CS)

16 (94.12)

53 (92.98)

0.73 (0.03 to 19.92)

08.  All multiple pregnancies (including prev. CS)

0

0

N/A

Intrapartum interventions for singleton pregnancies arising from assisted reproductive technologies.

Objectif : Déterminer si les grossesses monofœtales attribuables aux techniques de procréation assistée (TPA) sont associées à une hausse du recours à...
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