Interconception care for women with a history of gestational diabetes for improving maternal and infant outcomes
Abstract
Background
Gestational diabetes mellitus (GDM) is associated with adverse health outcomes for mothers and their infants both perinatally and long term. Women with a history of GDM are at risk of recurrence in subsequent pregnancies and may benefit from intervention in the interconception period to improve maternal and infant health outcomes.
Objectives
To assess the effects of interconception care for women with a history of GDM on maternal and infant health outcomes.
Search methods
We searched Cochrane Pregnancy and Childbirth's Trials Register (7 April 2017) and reference lists of retrieved studies.
Selection criteria
Randomised controlled trials, including quasi‐randomised controlled trials and cluster‐randomised trials evaluating any protocol of interconception care with standard care or other forms of interconception care for women with a history of GDM on maternal and infant health outcomes.
Data collection and analysis
Two review authors independently assessed study eligibility. In future updates of this review, at least two review authors will extract data and assess the risk of bias of included studies; the quality of the evidence will be assessed using the GRADE approach.
Main results
No eligible published trials were identified. We identified a completed randomised controlled trial that was designed to evaluate the effects of a diet and exercise intervention compared with standard care in women with a history of GDM, however to date, it has only published results on women who were pregnant at randomisation (and not women in the interconception period). We also identified an ongoing trial, in obese women with a history of GDM planning a subsequent pregnancy, which is assessing the effects of an intensive lifestyle intervention, supported with liraglutide treatment, compared with usual care. We also identified a trial that was designed to evaluate the effects of a weight loss and exercise intervention compared with lifestyle education also in obese women with a history of GDM planning a subsequent pregnancy, however it has not yet been published. These trials will be re‐considered for inclusion in the next review update.
Authors' conclusions
The role of interconception care for women with a history of GDM remains unclear. Randomised controlled trials are required evaluating different forms and protocols of interconception care for these women on perinatal and long‐term maternal and infant health outcomes, acceptability of such interventions and cost‐effectiveness.
PICOs
Plain language summary
Care prior to the next pregnancy for women diagnosed with gestational diabetes
What is the issue?
The aim of this Cochrane review was to look at the effects of specialised, targeted care given to mothers who have had a least one pregnancy affected by gestational diabetes. Does this sort of care improve the health of the mother and her baby, during and after her next pregnancy? We collected and analysed all relevant studies to answer this question (date of search: April 2017).
Why is this important?
Gestational diabetes (GD), also called gestational diabetes mellitus (GDM), is glucose intolerance arising during pregnancy. GDM can lead to health complications for the mother. These complications might include high blood pressure during pregnancy and at the birth, pre‐eclampsia (high blood pressure plus protein in the urine), and the development of type 2 diabetes in the future. The birth is more likely to be induced. The babies of mothers with GDM are more likely to be born by caesarean section, and to develop diabetes as children or young adults. Women who experience GDM are at risk of developing it again in a subsequent pregnancy.
If targeted care between the birth of one child and the next pregnancy – known as interconception care – reduces the incidence of GDM, then perhaps these health risks can be reduced, too.
Interconception care may include education, dietary and lifestyle advice, intervention with medication and careful monitoring of the mother’s health, focusing on testing for glucose tolerance.
What evidence did we find?
We searched for trials which looked at the health outcomes for women and babies after specific interconception care, and compared the outcomes for standard care (with no interconception care of this type). Our search identified one trial which has yet to issue a full set of results, plus two further trials; one of these is still underway and the other has yet to be published.
What does this mean?
Because there are no studies currently available, there is not enough evidence at present to say if interconception care for women with a history of GDM can help to improve the health of mothers and their infants. More high‐quality studies are needed, which assess both short‐ and long‐term health outcomes for women and their babies, as well as evaluating the impact on the health services.
Authors' conclusions
Background
Description of the condition
Gestational diabetes mellitus (GDM) is defined as 'carbohydrate intolerance resulting in hyperglycaemia of variable severity with onset or first recognition during pregnancy' (WHO 1999). This definition includes women who first present with type 1 or type 2 diabetes during pregnancy, or where diabetes was previously undetected. Although GDM typically resolves following birth, it is associated with adverse outcomes for both mother and infant, both in the perinatal period and in the long term.
In subsequent pregnancies of women with a history of GDM, one of the main issues is recurrence of GDM and the associated outcomes. Irrespective of subsequent pregnancies, other long‐term considerations for these women include the development of type 2 diabetes, metabolic syndrome and the risk of cardiovascular disease.
Epidemiology
The reported incidence of GDM varies between different populations and the method and criteria by which the diagnosis is made, with some studies estimating that between 1% and 28% of pregnancies are affected by GDM (Jiwani 2012). Despite variation in diagnostic criteria, there is widespread agreement that the prevalence of diabetes, including GDM, is increasing across the world, in line with the escalating prevalence of obesity. In women with a history of GDM, recurrence occurs in 30% to 84% of subsequent pregnancies (Kim 2007).
A number of risk factors have been linked to GDM, including a history of GDM or glucose intolerance (Kim 2007), family history of first‐degree relatives with GDM or type 2 diabetes, ethnicity (e.g. African, Hispanic, South or East Asian, Native American and Pacific Islander), advanced maternal age, maternal high or low birthweight, high parity, a past history of a macrosomic (large) baby or a stillbirth (Petry 2010), polycystic ovarian syndrome (Toulis 2009), and maternal overweight or obesity (body mass index (BMI) equal to or greater than 25 kg/m² or 30 kg/m², respectively) (Torloni 2009).
Many of these risk factors are unmodifiable background characteristics of the women. It is therefore unsurprising that women with a history of GDM are at an increased risk of recurrent GDM. In addition to a history of GDM in a previous pregnancy, other risk factors for recurrence include ethnicity, maternal age, prepregnancy obesity, weight gain between pregnancies, a short interpregnancy interval and the number of previous pregnancies affected by GDM (Gaudier 1992; Getahun 2010; Kwak 2008; Major 1998). Certain characteristics of the pregnancy affected by GDM have also been reported to increase the risk of recurrence, specifically, earlier diagnosis of GDM, insulin requirement for blood glucose control and higher infant birthweight (Gaudier 1992;Kwak 2008; MacNeill 2001; Major 1998).
Screening and diagnosis of gestational diabetes
There is little consensus on the most appropriate methods by which to screen and diagnose GDM. Screening methods include selective‐ (risk factor‐) based screening, or universal screening, commonly performed between 24 and 28 weeks' gestation, with the use of random or fasting blood glucose concentrations and a 50 g oral glucose challenge test. Diagnostic testing commonly involves either a 75 g or 100 g oral glucose tolerance test, with various diagnostic cut‐offs used. These are addressed in the Cochrane reviews 'Screening and subsequent management for gestational diabetes for improving maternal and infant health' (Tieu 2014) and 'Different strategies for diagnosing gestational diabetes to improve maternal and infant health' (Farrar 2015).
Women with a history of GDM are acknowledged as being at high risk for both GDM recurrence and type 2 diabetes, and it is suggested that women with a history of GDM may require greater monitoring for glucose intolerance during subsequent pregnancies, as such through early self‐monitoring of blood glucose, or an early oral glucose tolerance test (NICE 2015).
Clinical features
Maternal
GDM is usually diagnosed before women experience symptoms, such as polyuria, polydipsia or fatigue. GDM is associated with increased rates of caesarean birth and pre‐eclampsia (Dodd 2007). As mentioned above, women who develop GDM represent a subset of the population prone to developing subsequent type 2 diabetes, in addition to recurrent GDM in future pregnancies. Within 10 years of women developing GDM, approximately half develop type 2 diabetes (Kim 2002). Furthermore, there is increasing evidence that women with a history of GDM may also be at increased risk of cardiovascular disease and metabolic syndrome (Reece 2009; Reece 2010; Vohr 2008).
Infant
Excess insulin due to maternal hyperglycaemia acts in two ways on the fetus. Firstly, insulin promotes fat deposition due to the state of nutrient excess (Pedersen 1954; Whitelaw 1977). Insulin also acts as a growth factor, stimulating further growth of the infant in utero (Hunt 2007). Thus, fetal hyperinsulinaemia results in excessive growth of the fetus, leading to one of the major perinatal concerns in GDM, macrosomia (birthweight greater than 4000 g). Macrosomia may lead to birth trauma including shoulder dystocia, nerve palsies and fractures (Reece 2009; Reece 2010). GDM is associated with respiratory distress syndrome, neonatal hypoglycaemia (low blood glucose), hyperbilirubinaemia (high bilirubin levels), polycythaemia (excess red blood cells), and hypocalcaemia (low calcium) (Reece 2009; Reece 2010). In utero exposure to hyperglycaemia has long‐lasting effects on the infant, increasing their risk of future obesity and type 2 diabetes (Reece 2009; Reece 2010).
While there is relatively little reported on the effects of recurrent GDM on infants, infants born to mothers with recurrent GDM are likely to be larger, as measured by birthweight, incidence of large‐for‐gestational age, or macrosomia compared with infants born to mothers without recurrent GDM in a subsequent pregnancy (Spong 1998).
Management of GDM
The importance of management for women with GDM has been recognised (Crowther 2005; Landon 2009), and several Cochrane reviews have (or plan to) assess alternative management strategies for GDM (Alwan 2009), including lifestyle interventions (Brown 2017a), insulin (Brown 2016a), oral anti‐diabetic pharmacological therapies (Brown 2017b), exercise (Brown 2017c), dietary supplementation with myo‐inositol (Brown 2016b), and different intensities of glycaemic control (Martis 2016).
Description of the intervention
Interconception care may encompass a variety of interventions, including education, dietary and lifestyle advice, pharmacological intervention and active surveillance for illness and complications. It includes care between the birth of one child to the next pregnancy.
Internationally, clinical practice guidelines and consensus statements generally recommend postpartum assessment for continuing glucose intolerance after six to 12 weeks, by oral glucose tolerance testing to detect type 2 diabetes, and on a regular basis thereafter (i.e. every one to three years thereafter depending on other risk factors) (ACOG 2013; ADA 2017; CDA 2013; Metzger 2007; Nankervis 2014; NICE 2015). Despite such recommendations, a high proportion of women with previous GDM do not have testing for diabetes in the postpartum period (Blatt 2011). A Cochrane review evaluating 'Reminder systems for women with previous GDM to increase uptake of testing for type 2 diabetes or impaired glucose tolerance', showed low‐quality evidence supporting an increase in the uptake of testing for type 2 diabetes in women with previous GDM following the issue of postal reminders (Middleton 2014).
While often recommended, there is little evidence on what care women with a history of GDM should receive prior to a subsequent pregnancy. Clinical guidelines recommend that women be assessed preconceptually for a medical review and/or an oral glucose tolerance test, with early evaluation for glucose intolerance during pregnancy (ACOG 2013; NICE 2015). In addition to earlier identification and management of diabetes, interconception care after the postpartum period would ideally aim to target the modifiable risk factors for GDM, thus improving women's metabolic profiles.
How the intervention might work
In a survey of women with a history of GDM within the last five years, while 90% understood that previous GDM placed women at high risk of type 2 diabetes, only 16% believed that they themselves were at high risk of developing diabetes (Kim 2007b). This was partially explained by women planning to improve their behaviour in the future. When women considered the risks if they continued their current lifestyle, this risk perception rose to 39%. Importantly 85% of these women had plans for risk‐reducing behaviour (Kim 2007b). Another survey comparing women with children and a history of GDM with women with children without a history of GDM, found that those with a history of GDM were more likely to smoke and less likely to meet fruit and vegetable consumption recommendations (Kieffer 2006).
The interconception period provides an opportunity to provide advice on potential risks and possible interventions to improve health. Moreover, it provides the opportunity to identify undiagnosed pre‐existing diabetes. Since women with a history of GDM are at increased risk of diabetes, and pre‐existing diabetes in pregnancy is linked to poor maternal and infant health outcomes, it is important to identify and manage accordingly in the interconception period.
Risk factor reduction is a potential area of focus for these women, targeting modifiable risk factors such as maternal obesity where dietary and lifestyle interventions could be implemented and potentially benefit women with a history of GDM. Reducing maternal obesity itself may also lead to better maternal and infant health outcomes outside of its potential effect in the prevention of GDM. Regardless of whether women subsequently become pregnant, such interventions may improve the health of these women.
There is little information on the value of pharmacological agents such as oral anti‐diabetics for women with a history of GDM in the preconceptual period; assessed in the Cochrane review, 'Oral anti‐diabetic agents for women with pre‐existing diabetes mellitus/impaired glucose tolerance or previous gestational diabetes mellitus' (Tieu 2010b). The use of oral anti‐diabetic agents has been predominantly in the setting of polycystic ovarian syndrome or for prevention of type 2 diabetes in women with a history of GDM. 'Interventions for the prevention of type 2 diabetes in women with previous gestational diabetes' will be the focus of a planned Cochrane review (Li 2017).
Why it is important to do this review
Women with a history of GDM are recognised to be at high risk for recurrence in subsequent pregnancies, type 2 diabetes and cardiovascular disease, and therefore, for adverse maternal and infant health outcomes. While management of GDM is worthwhile, interconception care for these women also has the potential to improve maternal and infant health. Interconception care may also allow for detection and appropriate management of asymptomatic pre‐existing diabetes and provide an opportunity for risk factor reduction and, potentially, prevention of recurrent GDM and its sequelae.
Routine pre‐pregnancy care and preconception care for women with known diabetes mellitus are reviewed by the Cochrane reviews 'Routine pre‐pregnancy health promotion for improving pregnancy outcomes' (Whitworth 2009) and 'Preconception care for diabetic women for improving maternal and infant health' (Tieu 2010).
Objectives
To assess the effects of interconception care for women with a history of gestational diabetes mellitus on maternal and infant health outcomes.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs), including quasi‐RCTs and cluster‐RCTs. We plan to exclude cross‐over trials. We plan to exclude trials presented only as abstracts where information on risk of bias and primary or secondary outcomes cannot be obtained; we plan to reconsider these trials for inclusion once the full publication is available.
Types of participants
Women who have been diagnosed with gestational diabetes mellitus (GDM) in a previous pregnancy. Diagnosis of GDM made according to individual study criteria.
Types of interventions
Any protocol of care compared with no care and other forms of interconception care. Interventions may continue during pregnancy.
Types of outcome measures
For this update, we used the core outcome set agreed by consensus between review authors of Cochrane Pregnancy and Childbirth systematic reviews for prevention and treatment of gestational diabetes mellitus (GDM) and pre‐existing diabetes, which we adapted, as appropriate for this review question.
Primary outcomes
For women
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GDM (diagnostic criteria as defined in individual trials)
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Hypertensive disorders of pregnancy (including pre‐eclampsia, pregnancy‐induced hypertension, eclampsia)
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Caesarean section
For children
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Large‐for‐gestational age
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Perinatal mortality (stillbirth or neonatal death)
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Mortality or morbidity composite (e.g. death, shoulder dystocia, bone fracture or nerve palsy)
Secondary outcomes
For women
All women (interconception, and if pregnant, antenatal and postnatal)
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Adherence to the intervention
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Behaviour changes associated with the intervention
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Sense of well‐being and quality of life
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Views of the intervention
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Glycaemic control during/at the end of the intervention (e.g. HbA1c, blood glucose)
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Pregnancy
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Weight gain
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Body mass index (BMI)
Pregnant women
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Spontaneous abortion/miscarriage/therapeutic abortion
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Induction of labour
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Perineal trauma
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Placental abruption
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Postpartum haemorrhage
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Postpartum infection
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Breastfeeding
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Postnatal depression
Pregnant women with GDM
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Use of additional pharmacotherapy
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Hypoglycaemia
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Mortality
Longer term
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GDM in a subsequent pregnancy
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Type 1 diabetes mellitus
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Type 2 diabetes mellitus
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Impaired glucose tolerance
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Cardiovascular health (e.g. blood pressure, hypertension, cardiovascular disease, metabolic syndrome)
For children
Fetuses/neonates
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Stillbirth
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Neonatal death
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Gestational age at birth
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Preterm birth (before 37 weeks' gestation; before 34 weeks' gestation)
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Apgar score less than seven at five minutes
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Macrosomia
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Small‐for‐gestational age
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Birthweight and z score
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Head circumference and z score
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Length and z score
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Ponderal index
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Adiposity
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Shoulder dystocia
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Bone fracture
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Nerve palsy
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Respiratory distress syndrome
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Hypoglycaemia
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Hyperbilirubinaemia
Children/adults
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Weight and z scores
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Height and z scores
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Head circumference and z scores
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Adiposity (e.g. as measured by BMI, skinfold thickness)
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Cardiovascular health (e.g. blood pressure, hypertension, cardiovascular disease, metabolic syndrome)
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Education, employment and social status/achievement
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Type 1 diabetes mellitus
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Type 2 diabetes mellitus
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Impaired glucose tolerance
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Neurosensory disability
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Employment, education and social status/achievement
For the use of health services
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Number of hospital or health professional visits
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Number of antenatal visits or admissions
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Length of antenatal stay
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Neonatal intensive care unit admission
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Length of postnatal stay (mother)
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Length of postnatal stay (baby)
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Costs to families associated with the intervention
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Costs associated with the intervention
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Cost of maternal care
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Cost of infant care
Search methods for identification of studies
The following methods section of this review is based on a standard template used by Cochrane Pregnancy and Childbirth.
Electronic searches
We searched Cochrane Pregnancy and Childbirth’s Trials Register by contacting their Information Specialist (7 April 2017).
The Register is a database containing over 22,000 reports of controlled trials in the field of pregnancy and childbirth. For full search methods used to populate Pregnancy and Childbirth’s Trials Register including the detailed search strategies for CENTRAL, MEDLINE, Embase and CINAHL; the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service, please follow this link to the editorial information about Cochrane Pregnancy and Childbirth in the Cochrane Library and select the ‘Specialized Register ’ section from the options on the left side of the screen.
Briefly, Cochrane Pregnancy and Childbirth’s Trials Register is maintained by their Information Specialist and contains trials identified from:
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monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
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weekly searches of MEDLINE (Ovid);
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weekly searches of Embase (Ovid);
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monthly searches of CINAHL (EBSCO);
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handsearches of 30 journals and the proceedings of major conferences;
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weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts;
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scoping search of clinical trials registries (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP)).
Search results are screened by two people and the full text of all relevant trial reports identified through the searching activities described above is reviewed. Based on the intervention described, each trial report is assigned a number that corresponds to a specific Pregnancy and Childbirth review topic (or topics), and is then added to the Register. The Information Specialist searches the Register for each review using this topic number rather than keywords. This results in a more specific search set which has been fully accounted for in the relevant review sections (Studies awaiting classification; Ongoing studies).
Searching other resources
We searched the reference lists of retrieved studies.
We did not apply any language or date restrictions.
Data collection and analysis
For methods used in the previous version of this review, seeTieu 2013.
Two review authors independently assessed for inclusion the reports identified as a result of the search strategy. No studies were eligible for inclusion. We would have resolved any disagreement through discussion with a third person.
Full methods of data collection and analysis to be used in future updates of this review, if eligible studies are identified, are given in Appendix 1.
Results
Description of studies
The updated search of Cochrane Pregnancy and Childbirth's register identified nine reports, relating to one trial (Koivusalo 2016), which we have listed as awaiting further classification, and one report relating to one trial (ISRCTN76189107) which we have listed as ongoing.
Koivusalo 2016 recruited 788 women including 235 women who were not pregnant during their first study visit (women with a previous history of gestational diabetes mellitus (GDM) (187) or a pre‐pregnancy BMI ≥ 30 kg/m2 (48)), and assessed a diet and exercise intervention compared with standard care. To date, however, results have only been reported for the subset of women who were pregnant during the first study visit. See Characteristics of studies awaiting classification.
We identified one new ongoing trial (ISRCTN76189107), which plans to include 50 obese women with a previous history of GDM pre‐pregnancy, and assess the effects of an intensive lifestyle intervention supported with liraglutide treatment compared with standard care. In the previous version of this review we identified one additional trial (NCT00924599), which to date, has not been published (and is thus listed as ongoing). This trial planned to include 12 obese women with a history of GDM and to assess the effects of a pre‐pregnancy weight loss and exercise intervention compared with lifestyle education. See Characteristics of ongoing studies.
See: Figure 1.
Study flow diagram.
Risk of bias in included studies
No randomised controlled trials were included in the review.
Effects of interventions
No randomised controlled trials were included in the review.
Discussion
Summary of main results
One randomised controlled trial (Koivusalo 2016) was identified that was designed to assess the effects of interconception care on maternal and infant outcomes in women with a history of gestational diabetes mellitus (GDM), however to date, has only published results on women who were pregnant at randomisation, and not non‐pregnant women. A further two trials (ISRCTN76189107; NCT00924599), have been designed to assess the effects of lifestyle interventions for obese women with a history of GDM planning a subsequent pregnancy, however to date have not been published, or are ongoing.
Women with a history of GDM are at increased risk of recurrence of GDM in subsequent pregnancies, future impaired glucose tolerance and diabetes, cardiovascular disease and their sequelae. Given the potential poor outcomes identified in these women, they represent a group who could potentially benefit from intervention(s) aiming to prevent these outcomes. A number of interventions studied in women with a history of GDM after birth, most notably to increase follow‐up testing for impaired glucose tolerance or diabetes (Clark 2009), and interventions such as metformin and lifestyle modification to prevent type 2 diabetes (Ratner 2008) have demonstrated benefit. It remains uncertain how this may translate to interventions in the interconception period for the prevention of GDM recurrence.
In theory, the interconception period in these women represents a time in a high‐risk person's life for: identification and management of undiagnosed impaired glucose tolerance and type 2 diabetes; to initiate lifestyle interventions to potentially improve maternal and infant health outcomes; and to reinforce dietary and lifestyle behaviours for prevention of long‐term adverse health outcomes. No results from randomised controlled trials have been published relating to the effects of interventions in this interconception period for women with a history of GDM for improving health outcomes for women and their children. Given the potential benefits, it remains important to evaluate the effects of such interventions and identify the ideal form of intervention for these women.
