Document Detail

Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study.
Jump to Full Text
MedLine Citation:
PMID:  21998337     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome, taking into account maternal characteristics and assisted reproductive technology.
DESIGN: Population based cohort study.
SETTING: Singleton births registered in the Swedish medical birth register between 1995 and 2007.
PARTICIPANTS: By linkage with the Swedish patient register, 3787 births among women with a diagnosis of polycystic ovary syndrome and 1,191,336 births among women without such a diagnosis.
MAIN OUTCOME MEASURES: Risk of adverse pregnancy outcomes (gestational diabetes, pre-eclampsia, preterm birth, stillbirth, neonatal death, low Apgar score (<7 at five minutes), meconium aspiration, large for gestational age, macrosomia, small for gestational age), adjusted for maternal characteristics (body mass index, age), socioeconomic factors (educational level, and cohabitating with infant's father), and assisted reproductive technology.
RESULTS: Women with polycystic ovary syndrome were more often obese and more commonly used assisted reproductive technology than women without such a diagnosis (60.6% v 34.8% and 13.7% v 1.5%). Polycystic ovary syndrome was strongly associated with pre-eclampsia (adjusted odds ratio 1.45, 95% confidence interval 1.24 to 1.69) and very preterm birth (2.21, 1.69 to 2.90) and the risk of gestational diabetes was more than doubled (2.32, 1.88 to 2.88). Infants born to mothers with polycystic ovary syndrome were more prone to be large for gestational age (1.39, 1.19 to 1.62) and were at increased risk of meconium aspiration (2.02, 1.13 to 3.61) and having a low Apgar score (<7) at five minutes (1.41, 1.09 to 1.83).
CONCLUSIONS: Women with polycystic ovary syndrome are at increased risk of adverse pregnancy and birth outcomes that cannot be explained by assisted reproductive technology. These women may need increased surveillance during pregnancy and parturition.
Authors:
Nathalie Roos; Helle Kieler; Lena Sahlin; Gunvor Ekman-Ordeberg; Henrik Falconer; Olof Stephansson
Related Documents :
23565277 - Short placental telomere was associated with cadmium pollution in an electronic waste r...
19565417 - Teenagers and emergency contraception in the uk: a focus group study of salient beliefs...
11175527 - Maternal age, social changes, and pregnancy outcome in ribeirão preto, southeast brazil...
12680507 - Teenage pregnancies and abortions in finland in the 1990s.
7641747 - A correlative study of ultrasound calcaneal and dual-energy x-ray absorptiometry bone m...
594397 - The induction of labour by the intravenous infusion of prostaglandin f2alpha.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-13
Journal Detail:
Title:  BMJ (Clinical research ed.)     Volume:  343     ISSN:  1756-1833     ISO Abbreviation:  BMJ     Publication Date:  2011  
Date Detail:
Created Date:  2011-10-14     Completed Date:  2011-11-29     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8900488     Medline TA:  BMJ     Country:  England    
Other Details:
Languages:  eng     Pagination:  d6309     Citation Subset:  AIM; IM    
Affiliation:
Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital, H2:01, SE-171 76 Stockholm, Sweden. nathalie.roos@karolinska.se
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Age Factors
Apgar Score
Body Mass Index
Diabetes, Gestational / epidemiology
Epidemiologic Methods
Female
Gestational Age
Humans
Infant, Newborn
Infant, Small for Gestational Age
Maternal Age
Meconium Aspiration Syndrome / epidemiology
Obesity / epidemiology
Polycystic Ovary Syndrome / epidemiology*
Pre-Eclampsia / epidemiology
Pregnancy
Pregnancy Outcome*
Premature Birth / epidemiology
Reproductive Techniques, Assisted / statistics & numerical data
Socioeconomic Factors
Sweden / epidemiology
Young Adult
Comments/Corrections
Comment In:
BMJ. 2011;343:d6407   [PMID:  21998338 ]
J Midwifery Womens Health. 2012 Mar-Apr;57(2):202-3   [PMID:  22432496 ]
Nat Rev Endocrinol. 2012 Jan;8(1):2   [PMID:  22064500 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): BMJ
Journal ID (publisher-id): bmj
ISSN: 0959-8138
ISSN: 1468-5833
Publisher: BMJ Publishing Group Ltd.
Article Information
Download PDF
© Roos et al 2011
open-access:
Accepted Day: 11 Month: 9 Year: 2011
collection publication date: Year: 2011
Print publication date: Year: 2011
Electronic publication date: Day: 13 Month: 10 Year: 2011
Volume: 343E-location ID: d6309
ID: 3192872
PubMed Id: 21998337
Publisher Id: roon862417
DOI: 10.1136/bmj.d6309

Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study
Nathalie Roos12 Role: resident in obstetrics and gynaecology
Helle Kieler2 Role: associate professor and senior consultant in obstetrics and gynaecology
Lena Sahlin3 Role: associate professor and senior researcher
Gunvor Ekman-Ordeberg1 Role: professor and senior consultant in obstetrics and gynaecology
Henrik Falconer1 Role: PhD and senior consultant in obstetrics and gynaecology
Olof Stephansson2 Role: associate professor and senior consultant in obstetrics and gynaecology
1Department of Women’s and Children’s Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital, H2:01, SE-171 76 Stockholm, Sweden
2Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
3Department of Women’s and Children’s Health, Division for Reproductive Endocrinology, Karolinska Institutet, Stockholm, Sweden
Correspondence: Correspondence to: N Roos nathalie.roos@karolinska.se

Introduction

Polycystic ovary syndrome is one of the most common endocrine disorders, affecting about 5-15% of women of reproductive age.1, 2, 3 The condition is characterised by oligo-ovulation or anovulation, biochemical or clinical hyperandrogenism, and polycystic ovaries. According to the Rotterdam consensus from 2003, the presence of two of three of these criteria fulfils a diagnosis of polycystic ovary syndrome.4 The cause of polycystic ovary syndrome is not fully understood, but evidence of a genetic component has been recognised in family and twin studies.5 Oligo-ovulation or anovulation in women with polycystic ovary syndrome is a major cause of infertility, and such women might require ovulation induction or assisted reproductive technology to become pregnant.6 Changes to lifestyle can, however, improve the metabolic and endocrine consequences of having polycystic ovary syndrome, thus possibly improving infertility caused by anovulation.7

Evidence suggests that polycystic ovary syndrome has a negative impact on pregnancy outcomes, with an increased risk of gestational diabetes, hypertensive disease during pregnancy, and preterm birth.8 Available studies are, however, limited in size and have mainly included women undergoing assisted reproductive technology.8, 9 Consequently the extent to which the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome is attributed to the underlying disorder or infertility treatment is uncertain. We carried out a large nationwide cohort study of pregnant women, including pregnancies conceived spontaneously and by assisted reproductive technology to evaluate the risks of adverse pregnancy and birth outcomes in women with polycystic ovary syndrome.


Methods

From the Swedish medical birth register we created a cohort among women with singleton pregnancies giving birth between 1995 and 2007. Women with polycystic ovary syndrome are more likely to undergo assisted reproductive technology, with its higher frequency of twins and higher multiple births. Because twin and multiple pregnancies differ in fetal growth and duration of gestation and have a higher occurrence of complications during pregnancy we excluded such pregnancies from the study population.

Using the unique personal identification number assigned to each citizen at birth or immigration we linked data from the Swedish medical birth register with the Swedish patient and education registers.10 The Swedish patient register, established in 1964 (nationwide since 1987), includes information on dates of hospital admissions, discharges, and diagnoses classified according to ICD codes (international classification of diseases, 7-10th revisions). Since 2001 this registry has also included information on out-patient hospital visits. We recorded the date of the first diagnosis of polycystic ovary syndrome according to ICD codes: ICD-7, 275.20 and ICD-8, 256.90 (Stein-Leventhals syndrome); ICD-9, 256E; and ICD-10, E28.2. In the Swedish version of ICD-7 and ICD-8 the codes correspond to the formerly known Stein-Leventhals syndrome. For ICD-9 and ICD-10 the code is specified as polycystic ovary syndrome and Stein-Leventhals syndrome.

Register data

Data from the Swedish medical birth register include information on about 98% of births in Sweden, with information on the mother as well as the pregnancy, delivery, and neonatal period. Data are prospectively collected, starting at the woman’s first antenatal visit.11

We classified maternal age (years) at birth into four groups: 13-24, 25-29, 30-34, and ≥35. Body mass index was calculated (weight (kg)/(height (m)2) and the women categorised as lean (body mass index ≤19.9), normal weight (20.0-24.9), overweight (25.0-29.9), or obese (≥30.0). Parity was classified into nulliparous or parous women. Through linkage with the education register we obtained information on the number of years of formal education completed as of 1 January 2008, categorised as 11 or fewer or 12 or more. Cigarette smoking was recorded as none, 1-9 cigarettes daily, or 10 or more cigarettes daily. The Swedish medical birth register also contains information on whether the pregnancy was conceived by assisted reproductive technology or not and information on concurrent diseases such as diabetes mellitus and essential hypertension by checkbox as well as ICD-9 and ICD-10 codes. Pre-eclampsia was defined as a blood pressure reading of 140/90 mm Hg or more with proteinuria of more than 0.3 g over 24 hours. Gestational diabetes was, according to clinical practice, defined as plasma glucose levels of 12.2 mmol/L or more after oral glucose tolerance test (75 g glucose orally administered and plasma glucose measured after two hours) or fasting blood glucose levels of 7.0 mmol/L or more. Infants born small for gestational age were defined as having birth weights of less than 2 standard deviations below the mean for gestational age and sex of the infant. Similarly, large for gestational age was defined as a birth weight of more than 2 standard deviations above the mean for gestational age. Macrosomia was defined as a birth weight of 4500 g or more. Post-term pregnancy was defined as delivery at 42 weeks or more of gestation and preterm birth as delivery at less than 37 weeks of gestation, classified as moderately (32+0 to 36+6 weeks) and very preterm birth (<32 weeks). Stillbirth was defined as intrauterine fetal death after 28 weeks of gestation. A low Apgar score was defined as less than 7 at five minutes. Neonatal death was defined as death of the infant from 0 to 27 days after birth. The presence of meconium aspiration was obtained by diagnosis at discharge.

Statistical analysis

The main outcome measures were gestational diabetes, pre-eclampsia, preterm birth, stillbirth, neonatal death, low Apgar score, meconium aspiration, large for gestational age, macrosomia, and small for gestational age. Using logistic regression we estimated the risk of adverse pregnancy outcomes in relation to polycystic ovary syndrome by crude and adjusted odds ratios with 95% confidence intervals. Data were analysed using the SAS software version 9.2. We compared women with a diagnosis of polycystic ovary syndrome with women with no such diagnosis, taking into account possible confounders, such as maternal age, body mass index, parity, years of formal education, cigarette consumption, undergoing assisted reproductive technology, and calendar year of delivery. Absolute rates were standardised for difference in characteristics between women with and without polycystic ovary syndrome. In additional analyses we tested for residual confounding for the variables maternal age, body mass index, and parity by a finer categorisation and by analysing the continuous variables in a linear or linear-quadratic model.

Assisted reproductive technology refers only to in vitro fertilisation including intracytoplasmic sperm injection and not other forms of assisted reproductive technology such as ovulation induction or insemination.

Women tend to repeat pregnancy outcomes in successive births. Among women with polycystic ovary syndrome, 74.1% delivered one infant during the study period, 23.2% two infants, and 2.7% three or more infants. The corresponding frequencies among women without polycystic ovary syndrome were 53.0%, 38.1%, and 8.9%. Because observations are not independent in women who delivered more than once during the study period, we calculated estimates using clustered data in the generalised estimation equation method (PROC GENMOD). We used a formal interaction test in the logistic regression model to estimate the possible effect modification of assisted reproductive technology and body mass index on the association between polycystic ovary syndrome and preterm birth.


Results

A total of 1 195 123 singleton births between 1995 and 2007 were included in the cohort, with 3787 births among mothers with a diagnosis of polycystic ovary syndrome. Women with polycystic ovary syndrome were more likely to be nulliparous than women with no such diagnosis (53.0%, n=1990 v 43.8%, n=520 106, P<0.001). Undergoing assisted reproductive technology was more common in women with polycystic ovary syndrome (13.7%, n=510 v 1.5%, n=18 058, P<0.001). Women with polycystic ovary syndrome had an almost doubled prevalence of a body mass index greater than 25.0 (60.6%, n=1980 and 34.8%, n=348 340, P<0.001). Giving birth at advanced maternal age (>35 years) was more common in women with than without polycystic ovary syndrome (19.9%, n=753 and 17.6%, n=209 125, P<0.001). Women with polycystic ovary syndrome were more likely to have hypertensive disease and diabetes mellitus than women without polycystic ovary syndrome (table 1tbl1).

Tables 2tbl2 and 3tbl3 present absolute rates, absolute risk differences standardised for the difference in characteristics between women with and without polycystic ovary syndrome, and crude and adjusted relative risks for adverse pregnancy and birth outcomes.

In the adjusted analysis, women with a previous diagnosis of polycystic ovary syndrome had a higher risk of developing gestational diabetes than women with no such diagnosis (adjusted odds ratio 2.32, 95% confidence interval 1.88 to 2.88), whereas the adjusted risk difference was 1.81%. There was also a strong association between polycystic ovary syndrome and pre-eclampsia (1.45, 1.24 to 1.69) and very preterm birth (2.21, 1.69 to 2.90). Women with polycystic ovary syndrome had an 18% higher risk of undergoing caesarean section (both emergency and elective) compared with women without polycystic ovary syndrome (table 2).

Infants born to mothers with a previous diagnosis of polycystic ovary syndrome were more often large for gestational age (1.39, 1.19 to 1.62) and were also at increased risk of meconium aspiration (2.02, 1.13 to 3.61) and a low Apgar score at five minutes (1.41, 1.09 to 1.83). The risk of neonatal death was not significantly increased (1.58, 0.81 to 3.07; table 3). No residual confounding for maternal age, body mass index, and parity was found in sensitivity analyses (data not shown).

In a stratified analysis the adjusted odds ratio for preterm birth (<37+0 weeks) among women with polycystic ovary syndrome undergoing assisted reproductive technology was 1.08 (95% confidence interval 0.76 to 1.53) and among women with polycystic ovary syndrome conceiving spontaneously was 1.58 (1.33 to 1.79) (P=0.055 for interaction, table 4tbl4). The interaction between body mass index and polycystic ovary syndrome and the association with preterm birth was not significant.


Discussion

In the present population based study a diagnosis of polycystic ovary syndrome was associated with increased risks of adverse pregnancy outcomes that could not be attributed to the increased use of assisted reproductive technology or maternal characteristics such as advanced age or being overweight or obese.

Comparison with other studies

In previous studies preterm birth has been correlated to assisted reproductive technology, obesity, and polycystic ovary syndrome.8, 12, 13 This is in congruence with the findings of this study and furthermore we also found that the risk of preterm birth among women with polycystic ovary syndrome could not be explained by maternal characteristics such as advanced age, smoking, obesity, or use of assisted reproductive technology. There was an interaction between assisted reproductive technology and polycystic ovary syndrome for preterm birth. Since women with polycystic ovary syndrome often need assisted reproductive technology or ovulation induction to become pregnant, the risk of multiple births increases, which is associated with preterm birth. In previous reports the strongest predictor for preterm birth in women with polycystic ovary syndrome was multiple birth.14 A meta-analysis8 found a 75% increased risk of preterm birth in women with polycystic ovary syndrome, but when mean length of gestation was analysed women with polycystic ovary syndrome and controls did not differ.

We found a higher proportion of macrosomia and being large for gestational age among infants of mothers with polycystic ovary syndrome. This finding is controversial since the available studies have not established this association.14, 15, 16 It is well founded that maternal obesity is associated with increased birth weight in offspring17, 18 as well as glucose intolerance and gestational diabetes.19 Women with polycystic ovary syndrome are in general more overweight than women without the condition. The estimates in the present study were, however, adjusted for body mass index, suggesting that polycystic ovary syndrome may increase the rate of fetal growth independently. Women with polycystic ovary syndrome are, regardless of body mass index, at increased risk of developing gestational diabetes,8, 20 supported by our finding. Infants born to mothers with polycystic ovary syndrome were more likely to have low Apgar scores at five minutes and to experience meconium aspiration. These infants may be more susceptible to fetal distress during labour. However, there was no association with stillbirth, and the increased risk for neonatal death was not statistically significant. These findings need to be confirmed in future studies.

We observed a strong association between polycystic ovary syndrome and pre-eclampsia. Some studies have supported this finding,8, 21 and others not.14 It is well stated that women undergoing assisted reproductive technology are at increased risk of hypertensive disease during pregnancy,22, 23 which has been attributed to the underlying cause of infertility. In one study24 the risk of being born small for gestational age in the offspring of women with polycystic ovary syndrome was increased, whereas this could not be confirmed in other studies.14, 15, 16 We could not find any such correlation, suggesting that maternal polycystic ovary syndrome is not associated with growth restriction.

The increased risk of caesarean section among women with polycystic ovary syndrome we found does not correspond with the findings of other studies. In a meta-analysis,8 women with polycystic ovary syndrome showed a significantly higher rate of caesarean section (odds ratio 1.56, 95% confidence interval 1.20 to 2.02), but in a subgroup analysis restricted to studies of higher validity no significant risk was observed (0.92, 0.54 to 1.58). Obesity has been shown to be an independent risk factor for caesarean delivery.25 In the present study, however, obesity was accounted for in the adjusted analysis.

Women with polycystic ovary syndrome can conceive spontaneously but with a delayed fertile window since there is a tendency of regular menstrual cycles with advancing age.26 In the present study we found that women with polycystic ovary syndrome were slightly older than women without polycystic ovary syndrome. Advanced maternal age is strongly correlated with many of the adverse pregnancy outcomes in this study27; however, although we adjusted for maternal age in the multivariate analysis, a residual effect could still be possible.

Strengths and limitations of the study

A major strength of this study was the large sample size, making it possible to study rare pregnancy outcomes such as stillbirth, meconium aspiration, low Apgar scores at five minutes, and neonatal death. In this population based study we included women with pregnancies that were spontaneously conceived as well as conceived by assisted reproductive technology. Women with polycystic ovary syndrome according to the Rotterdam criteria,4 and not seeking medical assistance for irregular menstrual periods or infertility problems, might have been incorrectly classified as not having the disease. Such misclassification would lead to an underestimation of the association between polycystic ovary syndrome and adverse pregnancy outcomes. When the National Institutes of Health and Rotterdam criteria for polycystic ovary syndrome were compared, the prevalence was doubled.28, 29 This may imply an underestimation of women with polycystic ovary syndrome at the start of the study period, when the National Institutes of Health criteria was used. However, we adjusted for calendar period in the multivariate analyses. Furthermore, it is likely that we included women with more severe disease as exposed, and the findings may consequently not be generalisable to all women with polycystic ovary syndrome.

Possible pathophysiological mechanisms

The pathophysiological mechanisms behind the increased risk of adverse pregnancy outcomes among women with polycystic ovary syndrome are not fully known. In this study, polycystic ovary syndrome was associated with being overweight and obese, with an increased risk of macrosomia and large for gestational age infants, even after adjustments for body mass index. A higher prevalence of pre-eclampsia and gestational diabetes may account for increased fetal stress leading to preterm birth, low Apgar scores at five minutes, and meconium aspiration. Women with polycystic ovary syndrome have increased levels of androgens, which have been associated with the development of pre-eclampsia.30 Metformin treatment during pregnancy does not seem to lower maternal androgen levels but has been shown to decrease severe pregnancy and post-partum complications, which may be mediated by reduced uterine artery impedance.31, 32 Our results do not support the notion that assisted reproductive technology mediates adverse pregnancy outcomes among women with polycystic ovary syndrome. This finding is supported by a Norwegian study, which reported that adverse outcomes are attributable to the factors leading to infertility rather than to factors related to reproductive technology.33

Conclusions

In conclusion, women with polycystic ovary syndrome are at increased risk of adverse pregnancy and perinatal outcomes, which could not be explained by assisted reproductive technology. These women may need increased surveillance during pregnancy and parturition. Future research would benefit from focusing on glucose control, medical treatment, and hormonal status among women with polycystic ovary syndrome during pregnancy.

What is already known on this topic
  • Women with polycystic ovary syndrome undergoing assisted reproductive technology have increased risks of gestational diabetes, pre-eclampsia, and preterm birth
What this study adds
  • Irrespective of the use of assisted reproduction, polycystic ovary syndrome is associated with preterm birth, gestational diabetes, and pre-eclampsia
  • Infants born to mothers with polycystic ovary syndrome are more likely to have a low Apgar score at five minutes, have meconium aspiration, and be large for gestational age

Notes

Contributors: NR, HK, and OS designed the study. NR did the statistical analyses, reviewed the research, and wrote the introduction, methods, results, discussion, and conclusions. LS, GE-O, HF, HK, and OS helped write and review the methods, results, discussion, and conclusions. OS assisted in the statistical analyses. GE-O, LS, and OS are the guarantors.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: that this study received financial support from the Swedish Research Council (projects 73X-20137 (LS) 73X-14612 (GEO)) and the board of postgraduate education at Karolinska Institutet, Stockholm, Sweden (Karolinska Institutet Doctoral Student Financing Funds (KID)) (NR) for the submitted work, and that financial support was also provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet (LS); no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval: This study was approved by the Karolinska Institute’s local ethics committee.

Data sharing: No additional data available.

Notes

Contributors: NR, HK, and OS designed the study. NR did the statistical analyses, reviewed the research, and wrote the introduction, methods, results, discussion, and conclusions. LS, GE-O, HF, HK, and OS helped write and review the methods, results, discussion, and conclusions. OS assisted in the statistical analyses. GE-O, LS, and OS are the guarantors.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: that this study received financial support from the Swedish Research Council (projects 73X-20137 (LS) 73X-14612 (GEO)) and the board of postgraduate education at Karolinska Institutet, Stockholm, Sweden (Karolinska Institutet Doctoral Student Financing Funds (KID)) (NR) for the submitted work, and that financial support was also provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet (LS); no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

Ethical approval: This study was approved by the Karolinska Institute’s local ethics committee.

Data sharing: No additional data available.


References
1. Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome. Best Pract Res Clin Obstet GynaecolYear: 2004;18:737-54.15380144
2. Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol MetabYear: 2000;85:2434-8.10902790
3. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol MetabYear: 1998;83:3078-82.9745406
4. Rotterdam ESHRE/SRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum ReprodYear: 2004;19:41-7.14688154
5. Legro RS, Driscoll D, Strauss JF 3rd, Fox J, Dunaif A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci USAYear: 1998;95:14956-60.9843997
6. Rajashekar L, Krishna D, Patil M. Polycystic ovaries and infertility: our experience. J Hum Reprod SciYear: 2008;1:65-72.19562048
7. Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst RevYear: 2011;2:CD00750621328294
8. Boomsma CM, Eijkemans MJ, Hughes EG, Visser GH, Fauser BC, Macklon NS. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod UpdateYear: 2006;12:673-83.16891296
9. Heijnen EM, Eijkemans MJ, Hughes EG, Laven JS, Macklon NS, Fauser BC. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod UpdateYear: 2006;12:13-21.16123051
10. Ludvigsson JF, Otterblad-Olausson P, Pettersson BU, Ekbom A. The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. Eur J EpidemiolYear: 2009;24:659-67.19504049
11. Cnattingius S, Ericson A, Gunnarskog J, Kallen B. A quality study of a medical birth registry. Scand J Soc MedYear: 1990;18:143-8.2367825
12. Schieve LA, Meikle SF, Ferre C, Peterson HB, Jeng G, Wilcox LS. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J MedYear: 2002;346:731-7.11882728
13. Cnattingius S, Bergstrom R, Lipworth L, Kramer MS. Prepregnancy weight and the risk of adverse pregnancy outcomes. N Engl J MedYear: 1998;338:147-52.9428815
14. Mikola M, Hiilesmaa V, Halttunen M, Suhonen L, Tiitinen A. Obstetric outcome in women with polycystic ovarian syndrome. Hum ReprodYear: 2001;16:226-9.11157811
15. Haakova L, Cibula D, Rezabek K, Hill M, Fanta M, Zivny J. Pregnancy outcome in women with PCOS and in controls matched by age and weight. Hum ReprodYear: 2003;18:1438-41.12832369
16. Vollenhoven B, Clark S, Kovacs G, Burger H, Healy D. Prevalence of gestational diabetes mellitus in polycystic ovarian syndrome (PCOS) patients pregnant after ovulation induction with gonadotrophins. Aust NZ J Obstet GynaecolYear: 2000;40:54-8.
17. Baeten JM, Bukusi EA, Lambe M. Pregnancy complications and outcomes among overweight and obese nulliparous women. Am J Public HealthYear: 2001;91:436-40.11236410
18. Surkan PJ, Hsieh CC, Johansson AL, Dickman PW, Cnattingius S. Reasons for increasing trends in large for gestational age births. Obstet GynecolYear: 2004;104:720-6.15458892
19. Cok T, Tarim E, Bagis T. Isolated abnormal value during the 3-hour glucose tolerance test: which value is associated with macrosomia? J Matern Fetal Neonatal MedYear: 2011;24:1039-41.21247232
20. Radon PA, McMahon MJ, Meyer WR. Impaired glucose tolerance in pregnant women with polycystic ovary syndrome. Obstet GynecolYear: 1999;94:194-7.10432126
21. Fridstrom M, Nisell H, Sjoblom P, Hillensjo T. Are women with polycystic ovary syndrome at an increased risk of pregnancy-induced hypertension and/or preeclampsia? Hypertens PregnancyYear: 1999;18:73-80.10464001
22. Kallen B, Finnstrom O, Nygren KG, Otterblad Olausson P, Wennerholm UB. In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality. BJOGYear: 2005;112:1529-35.16225574
23. Jackson RA, Gibson KA, Wu YW, Croughan MS. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet GynecolYear: 2004;103:551-63.14990421
24. Sir-Petermann T, Hitchsfeld C, Maliqueo M, Codner E, Echiburu B, Gazitua R, et al. Birth weight in offspring of mothers with polycystic ovarian syndrome. Hum ReprodYear: 2005;20:2122-6.15802312
25. Sheiner E, Levy A, Menes TS, Silverberg D, Katz M, Mazor M. Maternal obesity as an independent risk factor for caesarean delivery. Paediatr Perinat EpidemiolYear: 2004;18:196-201.15130159
26. Hudecova M, Holte J, Olovsson M, Sundstrom Poromaa I. Long-term follow-up of patients with polycystic ovary syndrome: reproductive outcome and ovarian reserve. Hum ReprodYear: 2009;24:1176-83.19168874
27. Usta IM, Nassar AH. Advanced maternal age. Part I: obstetric complications. Am J PerinatolYear: 2008;25:521-34.18773378
28. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum ReprodYear: 2010;25:544-51.19910321
29. Tehrani FR, Simbar M, Tohidi M, Hosseinpanah F, Azizi F. The prevalence of polycystic ovary syndrome in a community sample of Iranian population: Iranian PCOS prevalence study. Reprod Biol EndocrinolYear: 2011;9:3921435276
30. Troisi R, Potischman N, Johnson CN, Roberts JM, Lykins D, Harger G, et al. Estrogen and androgen concentrations are not lower in the umbilical cord serum of pre-eclamptic pregnancies. Cancer Epidemiol Biomarkers PrevYear: 2003;12(11 Pt 1):1268-70.14652293
31. Salvesen KA, Vanky E, Carlsen SM. Metformin treatment in pregnant women with polycystic ovary syndrome—is reduced complication rate mediated by changes in the uteroplacental circulation? Ultrasound Obstet GynecolYear: 2007;29:433-7.17330831
32. Vanky E, Salvesen KA, Heimstad R, Fougner KJ, Romundstad P, Carlsen SM. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Hum ReprodYear: 2004;19:1734-40.15178665
33. Romundstad LB, Romundstad PR, Sunde A, von During V, Skjaerven R, Gunnell D, et al. Effects of technology or maternal factors on perinatal outcome after assisted fertilisation: a population-based cohort study. LancetYear: 2008;372:737-43.18674812

Notes

Cite this as: BMJ 2011;343:d6309


Tables
[TableWrap ID: tbl1] Table 1 

 Characteristics of women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007


Maternal characteristics No of births (rate %) P value*
Women with PCOS (n=3787) Women without PCOS (n=1 191 336)
Age (years):
 13-24 339 (8.95) 188 795 (15.85) <0.001
 25-29† 1180 (31.16) 390 088 (32.74)
 30-34 1515 (40.01) 403 303 (33.85)
 ≥35 753 (19.88) 209 125 (17.55)
 Data missing 0 25
Body mass index:
 ≤19.9 148 (4.53) 99 360 (9.91) <0.001
 20.0-24.9† 1140 (34.88) 554 456 (55.33)
 25.0-29.9 932 (28.52) 245 606 (24.51)
 ≥30.0 1048 (32.07) 102 734 (10.25)
 Data missing 519 189 180
Parity:
 0 1990 (52.55) 520 106 (43.66) <0.001
 ≥1† 1797 (47.45) 671 206 (56.34)
 Data missing 0 24
Education level (years):
 ≤11 2139 (56.69) 663 449 (56.11) 0.47
 ≥12† 1634 (43.31) 518 974 (43.89)
 Data missing 14 8913
Cigarette consumption (daily):
 None† 3192 (90.42) 988 375 (88.60) 0.003
 1-9 232 (6.57) 87 909 (7.88)
 ≥10 106 (3.00) 39 291 (3.52)
 Data missing 257 75 761
Assisted reproductive technology:
 Yes 515 (13.60) 18 020 (1.51) <0.001
 No 3272 (86.40) 1 173 316 (98.49)
Essential hypertension:
 Yes 26 (0.69) 3345 (0.28) <0.001
 No 3761 (99.31) 1 187 991 (99.72)
Diabetes mellitus:
 Yes 76 (2.01) 4596 (0.38) <0.001
 No 3711 (97.99) 1 186 767 (99.62)

*Wald test of overall effect (test of general heterogeneity).

†Reference group.


[TableWrap ID: tbl2] Table 2 

 Pregnancy outcomes in women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007


Pregnancy outcomes No of births (rate %) Standardised absolute risk difference* (%) in women with PCOS Crude odds ratio† (95% CI) Adjusted odds ratio† (95% CI) P value
Women with PCOS (n=3787) Women without PCOS (n=1 191 336)
Gestational diabetes:
 Yes 125 (3.30) 10 672 (0.90) 1.85 3.78 (3.16 to 4.52) 2.32 (1.88 to 2.88) <0.001
 No 3662 (96.70) 1 180 664 (99.10) 1.00 1.00
Pre-eclampsia:
 Yes 221 (5.84) 35 129 (2.95) 1.74 2.04 (1.78 to 2.34) 1.45 (1.24 to1.69) <0.001
 No 3566 (94.16) 1 156 207 (97.05) 1.00 1.00
Antepartum bleeding or placental complications:
 Yes 59 (1.56) 14 490 (1.22) 1.29 (0.99 to 1.66) 1.14 (0.85 to 1.53) 0.37
 No 3728 (98.44) 1 176 846 (98.78) 1.00 1.00
Caesarean section‡:
 Yes 846 (22.44) 174 298 (14.68) 2.75 1.69 (1.56 to 1.82) 1.18 (1.07 to 1.29) 0.001
 No 2924 (77.56) 1 013 112 (85.32) 1.00 1.00
 Data missing 0 30
Very preterm birth (<31+6 weeks)‡:
 Yes 65 (1.73) 7999 (0.67) 0.94 2.59 (2.02 to 3.31) 2.21 (1.69 to 2.90) <0.001
 No 3701 (98.27) 1 178 296 (99.33) 1.00 1.00
 Data missing 4 1145
Moderately preterm birth (32+0 to 36+6 weeks)‡§:
 Yes 226 (6.11) 50 352 (4.27) 1.38 1.46 (1.28 to 1.67) 1.31 (1.13 to 1.53) 0.0004
 No 3475 (93.89) 1 127 944 (95.73) 1.00 1.00
 Data missing 4 1145
Post-term birth (>42+0 weeks)‡:
 Yes 252 (6.69) 86 771 (7.31) −1.39 0.91 (0.80 to 1.03) 0.82 (0.71 to 0.95) 0.0069
 No 3514 (93.31) 1 099 524 (92.69) 1.00 1.00
 Data missing 4 1145

*Estimated for significantly associated outcomes.

†Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, assisted reproductive technology, and year of delivery.

‡Live births only.

§Risk compared with deliveries at 37 weeks and later.


[TableWrap ID: tbl3] Table 3 

 Perinatal outcomes in women with and without polycystic ovary syndrome (PCOS) giving birth to singleton pregnancies (1 195 123 total births) in Sweden, 1995 to 2007


Perinatal outcomes No of births (rate %) Standardised absolute risk difference (%) in women with PCOS† Crude odds ratio* (95% CI) Adjusted odds ratio* (95% CI) P value
Women with PCOS (n=3787) Women without PCOS (n=1 191 336)
Stillbirth:
 Yes 17 (0.45) 3896 (0.33) 1.38 (0.85 to 2.22) 0.90 (0.50 to 1.63) 0.73
 No 3770 (99.55) 1 187 440 (99.67) 1.00 1.00
Apgar score <7 at 5 minutes‡:
 Yes 71 (1.89) 12 909 (1.10) 0.54 1.74 (1.38 to 2.21) 1.41 (1.09 to 1.83) 0.0095
 No 3680 (98.11) 1 165 776 (98.90) 1.00 1.00
Data missing 19 8755
Neonatal death (0-27 days)‡:
 Yes 11 (0.29) 2179 (0.18) 1.59 (0.88-´to 2.88) 1.58 (0.81 to 3.07) 0.18
 No 3759 (99.71) 1 185 261 (99.82) 1.00 1.00
Meconium aspiration‡:
 Yes 13 (0.34) 1738 (0.15) 0.17 2.36 (1.37 to 4.07) 2.02 (1.13 to 3.61) 0.018
 No 3757 (99.66) 1 185 702 (99.85) 1.00 1.00
Large for gestational age:
 Yes 238 (6.32) 45 421 (3.84) 1.69 1.69 (1.48 to 1.93) 1.39 (1.19 to 1.62) <0.001
 No 3526 (93.68) 1 138 532 (96.69) 1.00 1.00
Data missing 23 7383
Macrosomia (birth weight ≥4500 g):
 Yes 194 (5.14) 47 937 (4.04) 1.29 (1.11 to 1.49) 1.16 (0.99 to 1.36) 0.072
 No 3582 (94.86) 1 139 030 (95.96) 1.00 1.00
 Data missing 11 4369
Small for gestational age:
 Yes 89 (2.36) 27 192 (2.30) 1.03 (0.84 to 1.27) 1.01 (0.81 to 1.27) 0.91
 No 3675 (97.64) 1 156 761 (97.70) 1.00 1.00
 Data missing 23 7383

*Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, assisted reproductive technology, and year of delivery.

†Estimated for significantly associated outcomes.

‡Live births only.


[TableWrap ID: tbl4] Table 4 

 Adjusted odds ratios of women with and without polycystic ovary syndrome (PCOS) and singleton preterm births (<37+0 weeks) undergoing assisted reproductive technology in Sweden, 1995 to 2007


Preterm birth Assisted reproductive technology* Rate Adjusted odds ratio† (95% CI) No assisted reproductive technology* Rate Adjusted odds ratio† (95% CI)
Women with PCOS Women without PCOS Yes No
Yes 41 1400 7.96 1.08 (0.76 to 1.53) 256 58 723 7.83 1.54 (1.33 to 1.79)
No 474 16 618 7.77 1.00 3012 1 113 426 5.01 1.00
Data missing 2 4 1167

*P=0.055 for interaction analysis for assisted reproductive technology and PCOS in relation to preterm birth.

†Adjusted for maternal age, parity, body mass index, years of education, cigarette consumption, and assisted reproductive technology.



Article Categories:
  • Research
Article Categories:
  • Epidemiologic Studies
  • Obesity (Nutrition)
  • Pregnancy
  • Reproductive Medicine
  • Child Health
  • Sexual Health
  • Metabolic Disorders
  • Health Education
  • Obesity (Public Health)
  • Health Promotion


Previous Document:  Adjuvant sequencing of tamoxifen and anastrozole is superior to tamoxifen alone in postmenopausal wo...
Next Document:  The Need for Standardization of Tacrolimus Assays.