Hormonal imbalance associated with PCOS and menopause affect glucose homeostasis and mental well being. Coordinated care and prepregnancy planning is necessary to ensure optimal outcomes for mother and baby. Planning for an optimal delivery begins in adolescence with diabetes education and sexual counselling.

Diabetes can develop during pregnancy, gestational diabetes. Most non-diabetic women are screened for diabetes during pregnancy so that blood glucose levels can be controlled to avoid the risks that having diabetes places on both mother and baby. Women particularly at risk are those with a history of diabetes in the family, diabetes during a previous pregnancy, or previous delivery of a large baby. There is increasing evidence that maternal hyperglycaemia has a lasting legacy for the child predisposing them to obesity in adolescence and Type 2 diabetes, and possibly memory deficits.

Polycystic Ovarian Syndrome (PCOS) is common, occurring in 6–10% of women in the reproductive age and 28% of obese women. Seventy five percent of women with PCOS are overweight or obese. PCOS has long term implications including menstrual irregularities, infertiliy, gestational diabetes (GDM), impaired glucose tolerance and insulin resistance, Type 2 diabetes, and emotional stress and body image concerns. Hyperinsulinaemia is associated with obesity and stimulates ovarian androgen production, insulin resistance, and cardiovascular disease.

Managing diabetes during pregnancy is challenging for the woman concerned and health professionals. Hormones released by the placenta predispose the mother to hyperglycaemia and increase the amount of glucose available to the fetus. Insulin sensitivity increases in the first trimester but insulin resistance develops in the second and third trimesters. The placental glucose transporter, GLUT-1, increases the transplacental glucose flux. The activity of GLUT-4 at the maternal cellular level decreases, which means glucose is not utilised by the mother and high levels cross the placenta where they are utilised by the fetus. This sets the scene for macrosomia and fetal abnormalities and makes vaginal delivery difficult (Hollingsworth 1992).

Prepregnancy counselling is essential to limit risks to mother and baby (Coustan 1997). Women who attend prepregnancy counselling have significantly lower risk of major fetal abnormalities (Ray et al. 2001). It should be provided to all women with diabetes of reproductive age, for example, at each annual review (Australian Diabetes in Pregnancy Society (ADIPS) 2005). Women with Type 2 diabetes and GDM are usually older than those with Type 1, are often overweight, higher parity, and belong to minority ethnic groups (Dornhurst et al. 1992). However, Type 2 diabetes is increasing in prevalence among adolescents and unwanted and unplanned pregnancy rates are high in this age group. In addition women are delaying childbirth, often until the mid-30s or 40s, which carries age-associated risks, and increases the likelihood that diabetes complications will be present and could affect the pregnancy. For example, age appears to be a significant factor in pregnancy-related MI although MI during pregnancy is rare (Karamermer & Ross-Hesselink 2007).

Coordinated multidisciplinary team care that includes as a minimum an obstetrician, endocrinologist, diabetes educator, dietitian, and paeditrician with experience managing diabetes is essential to optimal outcomes. Key management includes strategies to:

Complications can be reduced by careful monitoring and proactively managing the pregnancy especially controlling blood glucose and other risk factors. The following maternal complications are associated with maternal hyperglycaemia:

• Early: miscarriage, fetal abnormalities, difficulty performing ultrasound.
  
• Antenatal: hypertension and pre-eclampsia, hypoglycaemia. During delivery: Increased possibility that labour will need to be induced or Caesarian section will be required because of conditions such as macrosomia, shoulder dystocia. Increased risk of perioperative complications if surgery is required. For example hypoglycaemia can have serious consequences in women having epidural anaesthesia because the usual counter-regulatory response is blocked and because pregnant women are more prone to hypoglycaemia. Hypoglycaemia can retard reversal of hypotension in these situations (Marx et al. 1987). However, maternal glucose is often higher during Caesarian section than vaginal delivery (Andersen et al. 1989).
  
• Postpartum: maternal haemorrhage, infection, thrombosis, hypoglycaemia.
  
• Deterioration in existing diabetes complication especially renal disease and retinopathy and cardiovascular status. Cardiovascular disease is encountered more frequently because women ore older when they begin their families, a family history of cardiac disease, and have often have diabetes for >10 years. In addition, obesity is more common and smoking increases the risk. An ECG should be performed if chest discomfort develops especially if the woman has known cardiovascular risk factors (Karamermer & Roos-Hesselink 2007). Indications of heart disease include:
  
  
  
  • Serious or progressive dyspnoea (mild dyspnoea is usual)
    
  • Syncope on exertion
    
  • Chest pain/discomfort associated with exertion.

The maternal death rate is comparable to non-diabetic women when care is delivered by a qualified, collaborative multidisciplinary team, ∼0.5% of pregnancies in the UK (Chief Medical Officer’s Report 2000).

Consequences of maternal hyperglycaemia for the fetus include macrosomia, fetal distress, and birth injuries, which are largely preventable by good obstetric management and controlling maternal blood glucose levels. After delivery the baby may develop hypoglycaemia, hypothermia, hypocalcaemia, transient cardiomyopathy or other problems depending on the intrauterine conditions during pregnancy, delivery, and gestational age. The baby will need intensive monitoring initially, which might affect the bonding process.

Neonatal hypoglycaemia, defined as blood glucose <2.6 mmol/L up to 72 hours after birth, can cause significant morbidity and death if it is not recognised and treated effectively (Western Australian Center for Evidence Based Nursing and Midwifery 2006). The estimated incidence of newborn hypoglycaemia is between 1 and 5 per 1000 live births but may be up to 30% in at-risk infants (Hewitt et al. 2005). Hypoglycaemia is often present at birth and is usually transient in babies of non-diabetic mothers. Infants most at risk are:

• <2 kg or >4 kg at birth
  
• born before 37 weeks gestation
  
• <10th percentile for weight (small for gestational age)
  
• >90th percentile for weight (large for gestational age)
  
• retarded uterine growth
  
• born to mother with diabetes or GDM
  
• those with sepsis effectively (World Health Organisation (WHO 1997; Western Australian Center for Evidence Based Nursing and Midwifery 2006).

The maternal and baby’s blood glucose levels correlate at birth. Thus, the maternal blood glucose level is the most significant determinant of neonatal hypoglycaemia (Andersen et al. 1989). The signs of hypoglycaemia in the neonate are often non-specific and include high pitched crying, hypothermia and poor temperature control, sweating, refusing to feed or poor sucking, exaggerated Moro reflex, irritability, hypotonia, tachyapnoea, tachycardia, cyanosis, and lethargy. All of these signs also occur in other conditions.

Traditionally, hypoglycaemia is diagnosed in the presence of Whipple’s Triad: the presence of characteristic clinical signs of low blood glucose, low blood glucose, resolution of the signs once euglycaemia is re-established. However, the symptoms are unreliable in neonates, as can be seen from the preceding list. Having a high level of suspicion and performing a blood glucose test are essential. Once hypoglycaemia is corrected, babies are usually able to maintain blood glucose levels with normal breastfeeding on demand. Supplemental formula feeds may be required in the first 48 hours. Babies need to be kept warm and closely monitored in the neonatal nursery until they are stable.

Childhood obesity is increasing in many countries especially in ethnic minorities, see Chapter 1. The factors contributing to childhood obesity and associated consequences (insulin resistance, Type 2 diabetes, and diabetic complications) are debated. Genetic and environmental factors play a role (Dornhurst 2003) including the intrauterine environment during pregnancy, which has lasting effects on the child, the so-called Baker Hypothesis.

The fetus adapts structurally and functionally to reduced availability of essential nutrients. That is, under intrauterine ‘famine’ conditions available glucose is diverted to vital organs such as the brain and away from less immediately vital organs such as the pancreas. Insulin resistance develops in peripheral tissues to ensure a constant supply to vital organs and growth (birth weight) is retarded. The combination of reduced beta cell mass and pre-programming insulin-sensitive tissue to be insulin-resistant confers the risk of future diabetes on susceptible individuals (Baker et al. 1993). Low birth weight may be due to inadequate maternal intake and/or placental dysfunction. The association between Type 2 diabetes and low birth weight has been demonstrated in a number of population-based studies; however, the risk in developed countries with an adequate food supply is low (Boyko 2000) but may be higher in less affluent countries (Gray et al. 2002).

High birth weight is also associated with future risk of impaired glucose tolerance and Type 2 diabetes (Pettitt et al. 1996), which is likely to be a significant factor as the number of overweight women giving birth increases and they deliver higher birth weight babies. High birth weight is primarily due to maternal hyperglycaemia.

Memory deficits in childhood have also been attributed to poorly controlled maternal diabetes during pregnancy (De Boer 2007). De Boer suggested inadequate levels of iron and oxygen during development of the hippocampus (memory centre) in uterocontributed to the deficits, which were significant by age three and a half. She suggested available iron was used to manufacture haemoglobin and diverted away from the hippocampus, which is a metabolically active part of the brain that requires a lot of iron during prenatal neuronal development. The longer term implications of De Boer’s study are unknown and the research is ongoing. Significantly, the deficits were only noticeable on difficult memory tasks. The findings do underscore the importance of prenatal iron supplements and planning pregnancies.

Gestational diabetes (GDM) refers to carbohydrate intolerance of variable severity that first appears during pregnancy (Metzger 1998). GDM is the most common metabolic complication of pregnancy. Insulin resistance and hyperglycaemia develop as a result of the hormones produced by the placenta and declining beta cell function. The hormones oestradiol, cortisol and human placental lactogen rise during pregnancy to ensure that the fetus receives sufficient glucose to grow and develop normally. As a consequence, the mother’s cells become more resistant to insulin and the mother compensates by producing more insulin and using fat stores to produce energy for her own needs. GDM may in fact represent part of the continuum towards Type 2 diabetes.

It is recommended that all pregnant women be screened for diabetes between 24 and 28 weeks gestation, the time the placenta begins to produce large quantities of diabetogenic hormones. The most frequently used screening test is a non-fasting morning glucose challenge using 50 g glucose load. Levels ≥7.8 mmol/L at 1 hour identify 80% of women with GDM (American Diabetes Association 2004) or ≥8 mmol/L at one hour if 75 g glucose load is used. If the screening test is positive, a diagnostic fasting OGTT is usually performed using 75 g glucose solution. Diagnostic levels are baseline ≥5.5 mmol/L and ≥8 mmol/L at 2 hours (Hoffman et al. 1998) (100 g is used in the US). Women who do not meet the diagnostic criteria for GDM may still have babies with glucose-related macrosomia, respiratory distress, hyperbiluribinaemia, hypoglycaemia and require admission to neonatal intensive care. Adverse pregnancy outcome such as stillbirth, Caesarian section, and pre-eclampsia can also occur.

Usually the blood glucose returns to normal after the baby is delivered. However, approximately 40% of women with gestational diabetes will develop diabetes in later life. In addition, the baby is at increased risk of Type 2 diabetes. In most cases the OGTT is repeated 6–8 weeks after delivery and then on regular basis, for example, yearly, although many women do not return for follow up. A recent study of women with GDM in Sweden between 1995 and 2005 (n = 385) were tested for beta cell autoantibody markers to determine their risk of developing Type 1 diabetes (Nilsson et al. 2007). Six per cent tested positive for at least one islet cell antibody: ICA, GAD or IA-2A. These women were followed and autoantibody levels reanalysed. On OGGT was performed in women who did not develop diabetes. Fifty per cent of the autoantibody positive women developed Type 1 diabetes and 21% had IFG or IGT but none had developed Type 2 diabetes. The overall numbers in the study were small, but autoantibody testing may be indicated in some women who develop GDM.

Gestational diabetes can occur in any pregnancy, however, those women at highest risk are categorised as:

• Older then 30 years.
  
• Having a family history of diabetes or previous gestational diabetes or having had a large baby previously.
  
• Belonging to an at-risk ethnic group, for example, Vietnamese, Asian Indians, Australian Aboriginals.
  
• Being obese >12% of ideal bodyweight and having other features of the metabolic syndrome, see Section 1.6.

Diet and exercise are first line treatment of GDM to control maternal blood glucose and supply essential nutrients for normal fetal growth and development. Generally low GI foods are recommended where 40–50% calories come from complex high fibre carbohydrate, 20% from protein and 30–40% from unsaturated fats distributed evenly throughout the day. Nutrition counselling by a dietitian is recommended. Blood glucose goals are fasting <5.5 mmol/L and 1 hour postprandial <8 mmol/L. Insulin is indicated if these targets cannot be met.

Calorie restriction can predispose the woman and the fetus to ketonaemia and reduce psychomotor development and IQ between the 3rd and 9th year of age in the child especially during the second and third trimesters (Rizzo et al. 1995). Pregnant women who remain active have a 56% lower risk of developing glucose intolerance and GDM than inactive women (Zhang et al. 2006) and lower risk of Type 2 diabetes in the longer term (Artal & O’Toole 2003; Ceysens et al. 2007). There are no data for optimal weight gain during pregnancy (Metzger et al. 2007). The Fifth International Workshop-Conference on GDM (2003) recommended a relatively small weigh increase during pregnancy: ∼7 kg for obese women and up to 18 kg in underweight women.

Women at risk of GDM are advised to monitor their fasting and 2-hour postprandial blood glucose levels after each meal although there is no objective evidence to support the recommended frequency. CGM may be used to obtain a blood glucose pattern in some women, see Chapter 3. The aim of treatment is to keep blood glucose within the normal range (3–6.5 mmol/L), ensure the diet is appropriate, provide good obstetric care, and deliver the baby as close to term as possible.

Insulin will be required during pregnancy if blood glucose cannot be controlled using diet and exercise, generally when the fasting glucose is >7 mmol/L on three consecutive occasions but the duration of time on diet/exercise therapy before commencing insulin is unknown. Buchanan et al. (1994) recommended using insulin if the fetal abdominal circumference is >75th percentile for gestational age on ultrasound. However, a limitation of this method is that it provides a ‘snapshop’ rather monitoring continuous longitudinal fetal growth and should not be used alone especially given fetal macrosomia is related to maternal blood glucose levels. Insulin analogues are generally used, see Chapter 5 and the starting dose is calculated according to the woman’s weight generally ∼0.8 units/kg (non-obese), 0.9–1.0 units/kg (overweight and obese respectively).

Oral hypoglycaemic agents (OHAs) are contraindicated because they cross the placenta and cause neonatal hypoglycaemia and may have other unknown effects. However, metformin is used in Europe and South Africa and glibenclamide in South Africa without any reported fetal or maternal adverse outcomes. Although most other countries do not recommend OHA use during pregnancy (Metzger et al. 2007) the Metformin in Gestational Diabetes (MiG) (Rowan 2007) set up to compare metformin with insulin on perinatal outcomes suggests metformin is safe in the short term but may be contraindicated if the baby is small, or if the mother has pulmonary oedema or sepsis due to the risk of lactic acidosis, see Chapter 7. Metformin reduces absorption of vitamin B₁₂ but this can be overcome by supplementing with calcium.

Insulin is given as required during labour. Some obstetric units use insulin infusions to control hyperglycaemia, which may be exacerbated by the pain and stress of labour. Frequent blood glucose monitoring is required because insulin requirements fall dramatically after delivery and maternal hypoglycaemia is possible. The baby is prone to hypoglycaemia after delivery and should be monitored closely for 24 hours as indicated in the preceding section.

Encourage breastfeeding. Breastfeeding provides essential nutrition and immunity for the baby. It decreases the risk of obesity and Type 2 diabetes in later life in babies of women who develop GDM.

As stated, planning the pregnancy and achieving optimal health before becoming pregnant significantly improves outcomes. Insulin requirements vary throughout the pregnancy and frequent blood glucose monitoring is essential so doses can be adjusted appropriately.

The specific insulin dose depends on individual characteristics. Overweight women may be less sensitive to insulin and may require larger doses than lean women. NovoRapid is approved for use in pregnancy. There do not appear to be any safety issues using the other insulin analogues in pregnancy but clinical experience with Apidra and Detemir is not as extensive with the other analogues (Nankervis 2008 oral presentation).

Blood glucose testing before and one hour after each meal is ideal to help titrate insulin doses as needed. Insulin requirements usually increases by ∼20% in the first 5–6 weeks due to increased levels of progesterone and continues to rise slowly to weeks 9–11 at which time the placenta begins to produce progesterone and ovarian production ceases (Jovanovic 2004).

Progesterone levels may decline temporarily during the switch and consequently insulin requirements can drop especially in lean insulin-sensitive women. Hypoglycaemia risk increases. It may be necessary to perform 3 am blood glucose tests to determine whether hypoglycaemia occurs during the night. Progesterone levels increase again after ∼8–10 days and insulin requirements begin to increase and continue to do so during each trimester. At term when contractions begin insulin requirements drop because the available glucose is utilised to support uterine contractions. Three am blood glucose testing may be required again at this time.

After delivery insulin requirements generally drop significantly and only very low doses may be needed in the first 24–48 hours and eventually return to prepregnancy requirements. However, breastfeeding women usually require less long acting insulin because blood glucose is used to produce milk, but they may need more short-acting insulin at mealtimes. Hyperglycaemia may mean extra lactose in breast milk and cause problems for the baby such as diarrhoea and putting on excess weight.

Women with Type 1 diabetes may have hypertension as a consequence of nephropathy or hypertension may develop as a consequence of the pregnancy (American Diabetes Association 2000). Blood pressure must be carefully monitored and controlled to reduce the risk of pre-eclampsia, progression of renal disease and retinopathy. Medicines management can be complication because ACE inhibitors, β blocking agents and diuretics are generally contraindicated.

Women with Type 2 diabetes and hyperglycaemia may be commenced on insulin prior to conceiving to optimise blood glucose levels and improve pregnancy outcomes.

Women with Type 2 diabetes are usually commenced on insulin during pregnancy. As with Type 1 diabetes insulin requirements slowly increase over the course of the pregnancy. However, the typical temporary drop seen ∼9–11 weeks in women with Type 1 diabetes may not occur because women with Type 2 diabetes are generally insulin resistant. Insulin requirements are affected by hormone levels but also by arbohydrate intake and activity levels.

Women with Type 2 diabetes should monitor their blood glucose with the same frequency as those with Type 1 but are generally less prone to nocturnal hypoglycaemia.

After delivery women who were treated with diet and exercise may be able to resume that regimen but insulin is recommended if the woman decides to breast feed (ADIPS 2005). OHAs can be used but metformin is present in breast milk and the baby may develop hypoglycaemaia. Therefore, regular blood glucose testing may be needed, but could be stressful for the parents.