Pregnancy in women with diabetes remains complicated despite improvements in glucose control. This seems mainly due to the fact that normoglycemia is still outside of reach. Congenital malformations are already significantly increased in the case of HbA1c values of 2–4SD above the mean, and fetal macrosomia is increasing in incidence. The latter may be due to an increase in maternal body mass index (BMI), absence of cardiovascular complications, better placentation, and increased weight gain during pregnancy. Severe maternal hypoglycemia is a frequent complication during the first trimester of pregnancy. The outcome is generally poorer in the case of type-2 diabetes as compared to type-1, which is likely to be due to a higher incidence of maternal metabolic syndrome. In this article, preconceptional and antenatal management and the mode and timing of delivery are discussed, both for women with preexisting diabetes and for those with gestational diabetes mellitus.
Introduction
Pregnancies of women with diabetes continue to be at an increased risk of maternal and fetal complications. This mainly holds for type-1 and type-2 diabetes, but gestational diabetes mellitus (GDM) is also associated with an increased risk of complications. As GDM is a disease of the second half of gestation only, this is discussed separately.
In this article, the preconceptional and antenatal management of pregnancies are discussed as well as labor-related issues. Unfortunately, most of the items discussed are authority based and not evidence based, given the absence of proper randomized controlled trials in which different management strategies were compared.
Type-1 and type-2 diabetes: prepregnancy care and antenatal management
Care for women with preexisting diabetes should start before pregnancy. The lack of prepregnancy care is independently associated with an adverse outcome of pregnancy, but such care sometimes only reaches about 25% of the population, despite regional programs . Glucose should be regulated as strictly as possible and folic acid should be started before conception. Poor glucose control is associated with an increased risk of abortion and congenital malformations. The latter risk continues to increase with near-optimal glucose values (glycosylated hemoglobin (HbA1c) 2–4 standard deviation (SD) above the mean), and most population studies continue to show increased incidences of fetal malformations, to two to four times that in nondiabetic populations . In most cases, it is impossible to achieve real normoglycemia. Women should be counseled accordingly and informed about the possibility of an ultrasound diagnosis of morphological abnormalities in the first and second trimester of pregnancy. There is no scientific evidence regarding the dose of folic acid, but most authors advise a dose of 3–5 mg per day, given the increased risk of fetal neural tube defects in these women.
Retinal examination is advised in the case of longer-existing diabetes, and any form of retinopathy with retinal ischemia should be treated before pregnancy. With improved diabetes care, microvascular complications in these relatively young women become infrequent, but it is mandatory to check for (micro) albuminuria, among others, to differentiate between preeclampsia and preexisting renal problems in the case of hypertension in the course of pregnancy. Hypertension, mainly in obese women with type-2 diabetes, should be treated adequately; angiotensin-converting enzyme (ACE) inhibitors should be avoided as are angiotensin receptor blockers. Weight reduction before pregnancy in the case of maternal obesity should be discussed, although weight loss may be difficult. The BMI before pregnancy is related to the incidence of fetal macrosomia and in childhood and later obesity in their offspring . Table 1 summarizes all prepregnancy and antenatal care issues.
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Care for pregnant women with preexisting diabetes should preferably be given by a dedicated team of an endocrinologist, obstetrician, diabetes nurse, and dietician, preferably at one location.
The most important aspect of care during pregnancy is the establishment and maintenance of adequate glucose control. In early pregnancy, the largest risk concerns severe maternal hypoglycemia, which may occur in up to 40% of women with type-1 diabetes and hypoglycemic coma in about 20% of them, with maternal death in about 1 in 500 . Women with hypoglycemic events before pregnancy and those with the lowest HbA1C values are at the highest risks. Counseling should also involve driving a car, and frequent glucose measurements before and during a car trip are advised. The type and mode of insulin administration (injections and continuous subcutaneous insulin infusion) and of glucose control (intermittent vs. continuous glucose control) is out of the scope of this article.
The incidence of fetal macrosomia is related to maternal weight gain during pregnancy, in both diabetic and nondiabetic pregnancies . In women with type-1 diabetes, it has recently been shown that weight gain above the recommended limit may result in a striking increase in fetal macrosomia . Recommended weight gain according to the Institute of Medical Guidelines depends on the maternal BMI and is summarized in Table 2 . In severely obese nondiabetic women with a BMI >40, there is evidence that weight gain during pregnancy should be <5 kg for an optimal outcome with a low preterm delivery rate . Therefore, weight gain in pregnancy should be regularly assessed and, in conjunction with recommended weight gain, appropriate dietary advice should be given.
| BMI | Recommended weight gain | |
|---|---|---|
| kg | lb | |
| <18.5 | 12–18 | 28–40 |
| 18.5–25 | 11.5–16 | 25–35 |
| 25–30 | 6.8–11.4 | 15–25 |
| >30 | 5–9 | 11–20 |
A fetal anomaly ultrasound scan for morphological malformations is generally offered at a gestational age of around 20 weeks of gestation. However, such a scan may be preceded by a scan at 12–14 weeks, as many anomalies are already detectable at that age, including neural tube defects . Moreover, an enlarged fetal translucency may be indicative of malformations, including those of the heart .
Ultrasound fetal growth assessment is important for the detection of fetal macrosomia and of disproportional fetal growth with an increased abdominal/head circumference . A single scan has a restricted value given the inaccuracy in weight assessment, and a scan near term is less reliable than a scan earlier during the third trimester . Therefore, longitudinal growth assessment is likely to be superior to a single measurement late in pregnancy. Nowadays, around 50% of infants of women with type-1 diabetes and 30–40% of those with type-2 diabetes have a weight above the 90th centile, and most will have a disproportionate growth which includes infants with a birth weight within the normal range . This suggests an abnormal fetal growth in the majority of cases. The apparent increase in fetal macrosomia is likely to be due to an increase in maternal BMI, reduction in maternal vascular complications, better glucose control in early pregnancy resulting in a better placentation, increase in weight gain during pregnancy, and poorer control (especially postprandially) near term as women are not admitted routinely to the hospital anymore . Ultrasound assessment should also include the measurement of amniotic fluid volume and polyhydramnios may be indicative of inadequate blood glucose control.
In women with preexisting diabetes, there is still an increased incidence of intrauterine fetal death (1–3% as compared to about 0.4% in the normal population). This is usually an acute event related to fetal overgrowth relative to placental size and hyperglycemia resulting in anaerobic metabolism and lactate accumulation . It seems unlikely that routine weekly fetal heart rate recordings, as has been promoted, will detect these cases as the fetal metabolic state depends on the actual glucose levels. For long, we have asked women with preexisting diabetes about subjectively perceived fetal movements in relation to their glucose levels. Most women report no association between fetal movements and glucose values, but some indicate that they have noticed that movements disappear when they have increased glucose values (usually >10 mmol/l), reappearing again when glucose falls. We consider these women at an increased risk of fetal death and act accordingly (admission to hospital, optimal glucose regulation, fetal heart rate monitoring, and delivery when indicated), but we realize that this practice is only authority based. Fetal death does not seem to be related to macrosomia, which fits with the concept of impaired early placentation and later fetal overgrowth. Placental hormones in early pregnancy tend to be lower in women with preexisting diabetes than in control women . In a recent case of intrauterine fetal death at 34 weeks and a fetal weight at the 60th centile, first-trimester pregnancy-associated plasma protein A (PAPP-A) and placental growth factor appeared in retrospect to be far below the 10th centile (S. Kuc et al., unpublished observation). In the future, early markers of placentation taken together with fetal growth may identify women at the risk of stillbirth.
Doppler measurements of umbilical artery blood velocity waveform patterns in the risk assessment for fetal death do not seem to be useful in the case of preexisting diabetes, with early fetal growth restriction as the exception . The umbilical artery pulsatility index will generally be found to be normal as placental vascular development typically is normal, with fetal overgrowth exceeding placental capacity, and increased diffusion distances between the maternal intervillous space and fetal villi capillaries seem to be the underlying pathophysiological problem . Hypoxemia-induced blood flow redistribution (decreased middle cerebral/umbilical artery pulsatility index ratio) might be useful but has as yet been investigated insufficiently. The same may hold for ductus venosus velocimetry, which had been found to be related to adverse outcome, and may be associated with myocardial hypertrophy in these cases .
Type-1 and type-2 diabetes: prepregnancy care and antenatal management
Care for women with preexisting diabetes should start before pregnancy. The lack of prepregnancy care is independently associated with an adverse outcome of pregnancy, but such care sometimes only reaches about 25% of the population, despite regional programs . Glucose should be regulated as strictly as possible and folic acid should be started before conception. Poor glucose control is associated with an increased risk of abortion and congenital malformations. The latter risk continues to increase with near-optimal glucose values (glycosylated hemoglobin (HbA1c) 2–4 standard deviation (SD) above the mean), and most population studies continue to show increased incidences of fetal malformations, to two to four times that in nondiabetic populations . In most cases, it is impossible to achieve real normoglycemia. Women should be counseled accordingly and informed about the possibility of an ultrasound diagnosis of morphological abnormalities in the first and second trimester of pregnancy. There is no scientific evidence regarding the dose of folic acid, but most authors advise a dose of 3–5 mg per day, given the increased risk of fetal neural tube defects in these women.
Retinal examination is advised in the case of longer-existing diabetes, and any form of retinopathy with retinal ischemia should be treated before pregnancy. With improved diabetes care, microvascular complications in these relatively young women become infrequent, but it is mandatory to check for (micro) albuminuria, among others, to differentiate between preeclampsia and preexisting renal problems in the case of hypertension in the course of pregnancy. Hypertension, mainly in obese women with type-2 diabetes, should be treated adequately; angiotensin-converting enzyme (ACE) inhibitors should be avoided as are angiotensin receptor blockers. Weight reduction before pregnancy in the case of maternal obesity should be discussed, although weight loss may be difficult. The BMI before pregnancy is related to the incidence of fetal macrosomia and in childhood and later obesity in their offspring . Table 1 summarizes all prepregnancy and antenatal care issues.
