Undetected Maternal Diabetes Causing Multiple Severe Complications in a Newborn: A Case Report and Literature Review Free

A newborn girl presented with dyspnea during the first hour of life and was admitted to the NICU at Mother and Children Hospital in Nouakchott, Mauritania. Her mother was 30 years of age and had had four pregnancies and births. She had obesity, with a BMI of 37 kg/m², a family history of diabetes (type 1 or type 2), and irregular prenatal follow-up. During these follow-up visits, only fasting glucose was measured during the first and second trimesters and recorded as normal values. No oral glucose tolerance test (OGTT) was performed. The mother arrived in our center with 7 cm of cervical dilation. No prenatal infectious factors were identified, and the baby girl was born at term by vaginal delivery, with dystocia and laborious extraction.

The baby required 5 minutes of resuscitation at birth, with persistent tachypnea, and had an APGAR score of 6 at 5 minutes. Her birth weight was 4.8 kg, and her respiratory distress worsened, requiring oxygen supplementation and continuous positive airway pressure. Physical examinations discovered a left brachial palsy and edema in the right arm. Capillary testing revealed episodes of hypoglycemia, which resolved after 3 days of dextrose 10% infusion. A chest X-ray showed a right humerus fracture (Figure 1), and a heart echocardiogram at day 3 revealed moderate hypertrophic cardiomyopathy. An initial septic workup was negative, but intravenous (IV) antibiotics (ampicillin and gentamycin) that were started at birth were continued based on the lack of proper follow-up care of mother and to the respiratory signs with initial aggravation. No umbilical catheter or central line were inserted. These findings (i.e., macrosomia, respiratory distress, hypoglycemia, and hypertrophic cardiomyopathy) suggested that the baby was the infant of a mother with diabetes, and the obstetrical team was informed.

On day 2 of life, the baby developed cyanosis on the skin of the feet and legs, rapidly increasing from feet to buttocks, presenting heterogeneously and irregularly and complicated by skin gangrene (Figure 2). Doppler ultrasound of the lower limbs, followed by angiographic computed tomography (CT) confirmed thrombi of the infra-renal aorta and iliac arteries (Figure 3). Thrombophilia tests were normal, but an increase in C-reactive protein to 48 mg/L at day 5 of life was observed. No microbial agent was identified and antibiotic therapy was upgraded with cefotaxime and vancomycin. Surgical teams (a vascular surgeon and a pediatric surgeon) were consulted and performed procedures to remove the necrotic tissue without recommending any other intervention.

The baby required 3 weeks of hospitalization with vital support, close monitoring, skin ulcer care, analgesics, and anticoagulation by IV unfractioned heparin and then subcutaneous low-molecular-weight heparin overlapping with vitamin K antagonists. After significant clinical improvement, the baby was discharged but followed closely in the day hospital for several weeks and then in the outpatient clinic. Oral anti–vitamin K was given for 6 months. Clinical, biological, and radiological follow-up was conducted, and the baby eventually recovered and showed an excellent improvement on follow-up at 24 months (Figure 4).

Because of the suspicion that the baby’s mother had diabetes, the mother was advised to get screened for type 2 diabetes. She did not return to the obstetrical clinic until several months later, when she reported a history of intensive care unit admission for severe ketoacidosis.

1. Is it always possible and essential to distinguish between GDM and type 2 diabetes in pregnancy, and what are the differences in their effects on the fetus?

2. What are the main neonatal complications of maternal diabetes during pregnancy?

3. What risk factors indicate the need for diabetes screening?

4. What are the key recommendations for and challenges associated with carrying out appropriate screening and management of diabetes in pregnancy in developing countries?

Diabetes is a prevalent public health issue characterized by chronic hyperglycemia. GDM is a frequent metabolic complication during pregnancy with multifactorial etiology. It is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Typically, GDM is diagnosed between 24 and 28 weeks’ gestation without specific symptoms. The definition of GDM does not exclude the possibility that unrecognized glucose intolerance might have developed before pregnancy. Therefore, the term “hyperglycemia in pregnancy,” as suggested by the Endocrine Society, is considered more appropriate (5,8). The World Health Organization (WHO) recommends classifying hyperglycemia first detected during pregnancy as either “diabetes in pregnancy” or “GDM” (9).

Early screening of maternal diabetes is necessary to avoid severe short- and long-term complications for the mother, fetus, and neonate (5–7). The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommends universal screening for GDM. Diagnosis through this screening requires a single glucose measurement above the cutoff value (instead of two measurements) during the OGTT, thereby increasing the likelihood of detecting GDM (10). However, GDM is not routinely screened for in most low-resource settings in developing countries because of a shortage of resources and a lack of training. Additionally, there are sparce data on the prevalence of GDM, particularly in Africa (6). When risk factors for diabetes are present, pregnancy is an opportunity to screen and manage these cases early and effectively (7,9). In our case, two risk factors were evident: obesity and a strong family history of diabetes.

With pregnancies complicated by diabetes, there is an increased risk of polyhydramnios, macrosomia, and various short- and long-term complications for the mother, fetus, and neonate. These consequences include birth trauma, shoulder dystocia, higher rates of cesarean delivery, intrauterine growth restriction, encephalopathy, hypertrophic cardiomyopathy, respiratory distress, disordered postnatal metabolic and hematologic adaptation (neonatal hypoglycemia, hypomagnesemia, hyperbilirubinemia, hypocalcemia, and erythema), and iatrogenic complications (8,11). Thrombosis occurs more frequently in infants of mothers with diabetes and is likely related to polycythemia and hyperviscosity (11–14). Our patient experienced several of these severe complications.

In addition, when a mother has pre-pregnancy diabetes, the risks of congenital anomalies in offspring and maternal complications (nephropathy and retinopathy) increase. Although congenital anomalies do not occur at an increased rate in patients with GDM, recent studies have shown that GDM is associated with several subtypes of congenital anomalies in newborns, albeit to a lesser extent than with overt diabetes. Therefore, preconception counseling in women at risk for diabetes and GDM may help to prevent congenital anomalies (15). The severity of all these complications highlights the importance of establishing a program for screening diabetes in our setting, particularly because obesity remains a major public health problem for women in our country (16).

Long-term complications of GDM include diabetes and cardiovascular disease in mothers and obesity and diabetes in offspring (5,17,18). The risk of developing insulin-dependent diabetes by the age of 20 years in offspring of mothers with diabetes is at least seven times higher than in offspring of mothers without diabetes (11). Some studies indicate that infants born after pregnancy complicated by diabetes are at greater risk of brain injury, psychomotor delay, subtle neurological abnormalities, and electroencephalogram changes. However, studies of well-controlled diabetes during pregnancies have shown more favorable neurodevelopmental outcomes. It should also be noted that poor antenatal glycemic control and the presence of neonatal macrosomia increase the risk of obesity in later life (19,20).

In developing countries, there is often a lack of clear and applicable guidelines, and when guidelines are available, they often are not standardized. This case report appropriately highlights the need to both identify risk factors that should prompt early screening for type 2 diabetes in pregnant women and perform routine GDM screening in all obstetric patients. In various GDM public health programs in low-resource settings, different guidelines were used for screening and subsequently had to be adapted to fit into the local context (7,8).

Uniform strategies for screening and diagnosing GDM are lacking globally, but the WHO updated its recommendations in 2013 and included glucose cutoff values for GDM corresponding to those proposed by IADPSG. Simple guidelines that are easily applicable in certain low-resource settings, such as those proposed in some South Asian countries, are now being used in some developing countries to allow for early screening of GDM (21). The Societé Francophone du Diabète (French Diabetes Society) and the College National des Gynécologues et Obstétriciens Français (National College of French Gynecologists and Obstetricians) have proposed selective screening based on risk factors rather than universal screening. This proposed selective screening would involve measuring fasting blood glucose at the first visit for women with risk factors (6,22). This approach was taken for the mother of our patient but did not show any abnormality, demonstrating that relying on only fasting glucose testing during pregnancy may not always be sufficient.

The cornerstone of diabetes management during pregnancy is glycemic control throughout the pregnancy and intrapartum and postpartum periods, with prevention and follow-up of all at-risk patients (6). During pregnancy, the initial treatment for GDM is lifestyle interventions, along with frequent monitoring of glucose levels at home to ensure that glycemic targets are achieved. If the glycemic targets are not achieved with these interventions, medical therapy should be initiated. During labor and delivery, the goal is to maintain normoglycemia.

There is no universal recommendation on the ideal time for delivery for mothers with diabetes, and there is no consensus on whether induction of labor or expectant labor is more efficacious. Hospitals must have written protocols for the prevention and management of potential neonatal complications, including hypoglycemia, and for admission to the NICU if necessary. In addition, it is important to avoid iatrogenic problems such as the needless separation of mothers and babies or practices that impede successful breastfeeding (11). Moreover, breastfeeding should be encouraged because it may reduce maternal and neonatal risk for the later development of type 2 diabetes (5,23,24). Fasting glucose levels should be monitored for 24–72 hours after delivery, and an OGTT should be performed within 6–12 weeks after delivery. If the results are normal, subsequent OGTTs should be performed every 3 years to help detect women who remain at high risk or develop diabetes (5,6).

The mother of our patient most likely had undiagnosed type 2 diabetes given that, in addition to her baby’s presentation suggesting that she was an infant of a mother with diabetes, the mother experienced diabetic ketoacidosis soon after delivery. This situation reflects the difficulties in properly following high-risk patients in our health care system, where the woman did not return for planned follow-up. Fortunately, despite the severe complications of maternal diabetes, our infant patient is now experiencing normal growth and development.

• Severe neonatal complications can develop in infants of mothers with untreated diabetes.

• It is essential to identify risk factors that would prompt early screening for type 2 diabetes in pregnant women and to carry out routine screening for GDM in all obstetric patients.

• Reliance on fasting glucose measurement during pregnancy is not always sufficient for screening. Health authorities in developing countries should develop cost-effective, practical screening and management programs for GDM and type 2 diabetes during pregnancy, similar to those used for the prevention of anemia and gestational hypertension.

• The involvement of primary care structures in these protocols will improve their effectiveness, and planning for delivery of high-risk pregnancies in a center with trained staff for managing unexpected complications should also be prioritized.

No potential conflicts of interest relevant to this article were reported.

M.S. supervised the management of the case, researched and organized data, and wrote and edited the manuscript. H.A.-E. participated in the management of the case, collected data, and reviewed and revised the manuscript. Z.H. participated in the management of the case, collected data, and contributed to the discussion. H.-M.S.-O., A.E.G., and A.B. participated in the management of the case and collected data. A.W.M., K.E., A.A.-B., and F.A. contributed to the review of the obstetrical data and to the recommendations for the future. T.G., A.M., and L.H. participated in the management of the case and contributed to discussions and protocols regarding infants of mothers with diabetes. H.B. and K.B. participated in the management of the case. M.S. is the guarantor of this work and, as such, had full access to all the data in the case presentation and takes responsibility for the integrity of the data and the accuracy of the data analysis.