Pre-pregnancy care in diabetes – time for improvement

Diabetes mellitus is an umbrella term for a group of metabolic disorders that are universally associated with hyperglycaemia and affect one in every six pregnancies.¹ Pre-gestational diabetes refers to diabetes diagnosed prior to pregnancy and includes type 1 and type 2 diabetes, while gestational diabetes mellitus (GDM) is diagnosed during pregnancy using an oral glucose tolerance test (OGTT). Although GDM accounts for the majority of diabetes in pregnancy, pre-gestational diabetes affects approximately 1% of pregnant women.²

As both type 1 and type 2 diabetes are increasing in prevalence, clinicians require awareness of the risks associated with these conditions in pregnancy and approaches that can be taken prior to pregnancy in order to minimise these risks.³ Of particular relevance to Irish practice is the expected rise in prevalence of type 2 diabetes among women of childbearing age in line with rising obesity levels. 

Diabetes significantly increases the risk of adverse maternal and infant outcomes and women with pre-gestational diabetes have a two- to five-fold increased risk of congenital anomaly, stillbirth and neonatal death.^4,5,6 Key findings from the first Irish national audit of diabetes in pregnancy published earlier this year are outlined in Figure 1. 

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Of significant concern are high rates of Caesarean delivery (65%) and neonatal intensive care unit admissions (47%) among women with diabetes and their infants.⁷ Another key point is that while women with type 2 diabetes are often perceived as having less risk, they actually experience similar complication rates to women with type 1 diabetes and should receive equal attention before, during and after pregnancy.⁸ Women with GDM have a 30% increased risk of requiring a caesarean delivery and a 50% increased risk of developing pregnancy-induced hypertension. Their infants are twice as likely to require admission to a neonatal intensive care unit, develop neonatal hypoglycaemia or respiratory distress.^9,10

This article will focus on pre-pregnancy care, which can improve pregnancy outcomes and is particularly helpful for women with type 1 and type 2 diabetes. 

Rationale for pre-pregnancy care

The first trimester of pregnancy is a critically important time for foetal development and there is a clear association between higher glucose levels in early pregnancy and adverse pregnancy outcomes. For example, women with a HbA1c > 7.5% at the booking antenatal visit have a nine- fold increase in major congenital malformations.¹¹

In order to have good glycaemic control during these early weeks of pregnancy, women with pre-existing diabetes benefit from pre-pregnancy interventions.¹² This may be delivered in the form of pre-pregnancy care, which is targeted support, and additional clinical care offered to women with diabetes who are planning pregnancy.¹³ Ideally, all aspects of diabetes-related health are addressed during this time.¹⁴

Components of pre-pregnancy care

In Ireland, pre-pregnancy care is generally delivered in a dedicated clinic run by a multidisciplinary team involving an endocrinologist, nurse/midwife specialist in diabetes and dietitian.¹⁵ Women are reviewed frequently (every 1-3 months) and it takes six months on average to adequately prepare for pregnancy.¹⁶ The approach to care should be positive and attendees should feel empowered to self-manage their diabetes. Women should be reassured that while it might be challenging to achieve ‘optimal’ preparation status, any improvements in HbA1c and other goals will improve the chances of a good pregnancy outcome.

The following areas are typically addressed (see Table 1):

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Glycaemic control 

The ideal pre-pregnancy HbA1c is 48mmol/mol (6.5%) or less; however, this target may be increased if there is a significant risk of hypoglycaemia. In order to reach this goal, women generally need to perform up to seven capillary glucose levels per day. We encourage women to aim for a fasting glucose of < 5.3mmol/L and a one-hour post-meal glucose of < 7.8mmol/L. 

While a recent randomised controlled trial did not show any benefit of continuous glucose monitoring in women planning pregnancy, use of this technology during pregnancy was associated with improved neonatal outcomes. Bearing this in mind, specialist providers may elect to initiate continuous glucose monitoring pre-pregnancy in select circumstances.¹⁸ Women should understand how to self-manage hypoglycaemia and immediate family members should be familiar with and have access to glucagon, as the risk of hypoglycaemia increases with tightening of glycaemic control. 

Medication review

Medications commonly prescribed in the setting of diabetes such as statins, angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARB) are not considered safe in pregnancy and need to be discontinued. Metformin is safe in pregnancy and may be continued but all other oral glucose-lowering agents should be discontinued.² In relation to rapid-acting insulin, aspart and lispro are both safe options.¹²

Isophane insulin (NPH) has been traditionally the first choice for longer-acting insulin;² however we recommend that women who are well-established on the long-acting insulin analogues detemir and glargine can be continued due to extensive clinical experience.¹² There are no data regarding safety of newer analogue insulins or injectable GLP-1 analogues in this setting. 

Blood pressure assessment

The target blood pressure for the majority of women is < 130/80mmHg. The betablocker labetolol may be used in pregnancy and calcium channel blockers such as nifedipine are also favoured. Methyldopa is used frequently, but postural dizziness is a frequent side effect.¹⁵

Screening and management of diabetes complications

Women should be evaluated and treated for retinopathy prior to embarking on pregnancy, as there is a risk of deterioration once pregnancy is established.¹⁹ Those who have large reductions in HbA1c during pregnancy in an attempt to improve foetal outcomes are at greatest risk of retinopathy progression.¹⁹ This supports the aim of achieving gradual, sustainable glucose improvements pre-pregnancy.

Renal assessment involves measurement of a urine albumin:creatinine ratio with specialist referral if > 30mg/mmol. Likewise, if the estimated glomerular filtration rate (eGFR) is < 45ml/min/1.73m2, referral to a nephrologist should take place.

In those women with additional risk factors such as a positive family history; smoking history or advanced age, specialised screening for cardiovascular disease should take place.

Screening and managing additional autoimmune conditions

Autoimmune thyroid disease, coeliac disease and vitamin B12 deficiency are all increased in those with type 1 diabetes and may be identified by a clinical history, examination and laboratory testing. Metformin is associated with vitamin B12 deficiency and so women receiving this medication should be screened.²⁰

Supplementation and dietary review

Women with diabetes should receive folic acid 5mg daily for three months prior to attempting conception with the aim of reducing the incidence of neural tube defects, which occur more frequently with diabetes.^17,21 This higher dose requires a prescription. Approximately 1,000mg of elemental calcium and 600 IU of vitamin D per day should be incorporated into the diet or taken as supplementation as this is required to support neonatal bone health once pregnant.³

Obesity is common in individuals with type 2 diabetes and prevalence is increasing among those with type 1 diabetes.³ Obesity is an independent risk factor for adverse outcomes, particularly congenital anomalies. A recent population-based study in Sweden demonstrated that major cardiac congenital anomalies including atrial septal defect, aortic arch defects and transposition of the great arteries increased with maternal body mass index (BMI).²² Ideally, all women with diabetes would have assessment by a registered dietitian prior to pregnancy. However, those with overweight or obesity will especially benefit from a specialised nutrition plan that targets a 5-10% loss in body weight prior to conception.³

Benefits of pre-pregnancy care

There is extensive literature describing the benefits of pre-pregnancy care for women with diabetes worldwide.²³ In Ireland, the Atlantic Diabetes in Pregnancy (DIP) research group designed, implemented and assessed the effectiveness of a regional pre-pregnancy care programme involving clinical sites along the Irish Atlantic Seaboard. 

Women who attended the programme were better prepared for pregnancy with lower HbA1c levels; and their infants had lower rates of congenital malformations (1% versus 5%) and admission to neonatal intensive care units (44% versus 62%). The programme was also economically favourable and due to the success of this programme, pre-pregnancy care clinics are now available routinely in the West of Ireland.¹⁶

Unfortunately, pre-pregnancy care is not easily available to all women with diabetes in Ireland and the recent Irish national audit revealed that just 22% of women with diabetes attended formal pre-pregnancy care.⁷ Recently in the UK, an alternative model of pre-pregnancy care was piloted. In this approach, written and electronic educational material and group educational events were used to deliver community-based care for women with diabetes. This programme was well-received and attendees were better prepared for pregnancy.²⁴

Women with prior GDM

Women with GDM in one pregnancy are more likely to have GDM in a future pregnancy. While pre-pregnancy care for women with a history of GDM tends to be less structured than for established diabetes, if possible, risk factors for GDM (see Table 2) should be explored and addressed prior to embarking on a future pregnancy. At a minimum, type 2 diabetes should be ruled out pre-pregnancy in women with a history of GDM.

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Unplanned pregnancy

Although women with diabetes are encouraged to plan pregnancy, approximately 50% of pregnancies are unplanned. It is important that when pregnancy occurs, women with diabetes have urgent specialist review in order to provide the necessary support and make appropriate treatment changes as soon as possible. 

Conclusions

Pre-pregnancy care is effective in reducing adverse pregnancy outcomes in women with established diabetes. Women with GDM in a prior pregnancy should receive support to reduce their risk of GDM in a subsequent pregnancy. It is hoped that future resource allocation will make this care available to all women with diabetes. 

References

1. Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018; 138: 271-281
2. National Institute for Health and Care Excellence. Type 1 diabetes in adults overview. 2016; available at: http://pathways.nice.org.uk/pathways/type-1-diabetes-in-adults. Accessed July 31, 2018
3. Alexopoulos AS, Blair R, Peters AL. Management of Preexisting Diabetes in Pregnancy. A review. JAMA 2019;18:1811-1819
4. Macintosh MC, Fleming KM, Bailey JA, et al. Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ. 2006; 333: 177
5. Persson M, Norman M, Hanson U. Obstetric and perinatal outcomes in type 1 diabetic pregnancies: A large, population-based study. Diabetes Care. 2009; 32: 2005-2009
6. Evers IM, de Valk HW, Visser GH. Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ. 2004; 328: 915
7. Egan AM, Brassill MJ, Brosnan E, et al. A National Diabetes in Pregnancy Audit – aiming for best outcomes for women with diabetes. Diabetic Med. 2019 [epub ahead of print]
8. Owens LA, Sedar J, Carmody L, Dunne F. Comparing type 1 and type 2 diabetes in pregnancy- similar conditions or is a separate approach required? BMC Pregnancy Childbirth. 2015; 69
9. O’Sullivan EP, Avalos G, O’Reilly M, et al. Atlantic Diabetes in Pregnancy (DIP): the prevalence and outcomes of gestational diabetes mellitus using new diagnostic criteria. Diabetologia. 2011; 54: 1670-1675
10. Owens LA, Egan AM, Carmody L, Dunne F. Ten years of optimizing outcomes for women with type 1 and type 2 diabetes in pregnancy - the Atlantic DIP experience. J Clin Endocrinol Metab. 2016;101:1598-1605
11. Temple R, Aldridge V, Greenwood R et al. Association between outcome of pregnancy and glycaemic control in early pregnancy in type 1 diabetes: population based study. BMJ. 2002; 325: 1275-1276
12. Egan A, Dunne F. Tips from the shop floor: pre-pregnancy care for women with diabetes. British Journal of Hospital Medicine. 2016; 77: C191-193
13. Murphy HR, Roland JM, Skinner TC, et al. Effectiveness of a Regional Prepregnancy Care Program in Women With Type 1 and Type 2 Diabetes Benefits beyond glycemic control. Diabetes Care. 2010;33:2514-2520
14. Wahabi HA, Alzeidan RA, Bawazeer GA, et al. Preconception care for diabetic women for improving maternal and fetal outcomes: a systematic review and meta-analysis. Bmc Pregnancy and Childbirth. 2010;10:63
15. Egan AM, Murphy HR, Dunne FP. The management of type 1 and type 2 diabetes in pregnancy. QJM. 2015;108:923-927
16. Egan AM, Danyliv A, Carmody L, et al. A Prepregnancy Care Program for Women With Diabetes: Effective and Cost Saving. J Clin Endocrinol Metab. 2016; 101: 1807-1815
17. Health Service Executive. Guidelines for the Management of Pre-gestational and Gestational Diabetes Mellitus from Pre-conception to the Postnatal period. 2010 www.hse.ie/eng/services/publications/nursingmidwifery%20services/onsdguidelinesgestationaldiabetes.pdf Accessed July 31, 2018
18. Feig DS, Donovan LE, Corcoy R et al. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. Lancet. 2017; 10110:2347-2359
19. Egan AM, McVicker L, Heerey A, et al. Diabetic retinopathy in pregnancy: a population-based study of women with pregestational diabetes. J Diabetes Res. 2015; 2015: 310239
20. Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP. Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: the National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012; 35: 327-333
21. Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013; 98: 4227-4249
22. Persson M, Razaz N, Edstedt Bonamy AK, Villamor E, Cnattingius S. Maternal Overweight and Obesity and Risk of Congenital Heart Defects. J AM Coll Cardiol. 2019; 1: 44-53
23. Wahabi HA, Alzeidan RA, Esmaeil SA. Pre-pregnancy care for women with pre-gestational diabetes mellitus: a systematic review and meta-analysis. Bmc Public Health. 2012; 12: 792
24. Yamamoto JM, Hughes DJF, Evans ML, et al. Community-based pre-pregnancy care programme improves pregnancy preparation in women with pregestational diabetes. Diabetologia. 2018 [Epub ahead of print]