Twin pregnancy after kidney transplant – the insight of the prenatal and postnatal problems based on a case report

Introduction

Data has shown that the pregnancy rate is higher after a kidney transplant (KT) and the miscarriage rate is lower than in the general population. However, the risk of adverse pregnancy outcomes such as preeclampsia, cesarean section and preterm delivery are much higher in the KT group than in the general population [1, 2]. The most important determinant of adverse pregnancy outcomes is kidney function impairment not the fact of having KT [3]. The rate of multiple pregnancies in patients with chronic kidney disease is around 6%. However, these pregnancies were associated with higher risk of adverse outcomes. Apart from preterm delivery, higher frequencies of small for gestational age (SGA), perinatal and neonatal mortality were also observed [4].

CASE REPORT

A 35-year-old patient three years after a kidney transplant due to glomerulonephritis on immunosuppressant therapy, conceived spontaneously a dichorionic diamniotic twin pregnancy (DCDA). A previous pregnancy (2012) was complicated by chronic kidney disease (glomerulonephritis) and ended by c-section in 27 weeks of pregnancy because of HELLP syndrome. The neonate died a few days after delivery. In the current pregnancy, the patient was admitted to the hospital (Tertiary Center) due to acute atrial fibrillation episode in 21 weeks of gestation. On admission, she had low blood pressure and complete arrhythmia. Blood results were within the normal range. She needed an electrical cardioversion and was put on heparin. On the ultrasound, DCDA twin pregnancy was confirmed, additionally, severe fetal growth restriction (FGR) with oligohydramnios of twin two was diagnosed. Furthermore, the pregnancy was complicated by hypertension and a change in hypertensive medication was needed due to poor control, her blood pressure was nicely controlled by labetalol. As an immunosuppressant therapy, she was receiving azathioprine, tacrolimus, and prednisone. In the subsequent ultrasounds during hospitalization deterioration of the condition of the growth restricted twin was observed. Due to poor medical and obstetrical history, the multidisciplinary team with the patient made the decision not to end the pregnancy due to the growth restricted fetus indication until 28 weeks, to improve chances of having at least one child. Further close monitoring of the mother and twin’s condition during a stay in hospital was performed. At 27 weeks and 5 days, bleeding from the vagina was noted, on the ultrasound abruption of the placenta of the twin, which was growing normally, was confirmed and an emergency c-section was performed. The steroids for lung maturation and neuroprotection were given one day before the c-section. The weight of twin one was 1200 g, with an Apgar score of 6-9-9-9 points and twin two (intrauterine growth restricted) 620 g, Apgar score 4-6-7-7 points. Both twins were admitted to the Neonatal Intensive Care Unit. A summary of the postnatal period in both twins is provided in Table 1. A 12-month follow up revealed normal psychomotor development in twin one (normally growing twin) with weight and height on the 50th centile. He caught up with his peers who were born appropriate for gestational age. In twin two (born below 3rd centile) developmental delay was observed. His weight and height were below the 10th centile. The developmental milestones of twin 2 are presented in Table 2.

DISCUSSION

The rate of successful pregnancies after kidney transplant is 61%, however, 36% of these are preterm deliveries and 16% are extremely preterm (below 28 weeks) due to severe hypertension, preeclampsia, abruption of the placenta or severe fetal growth restriction. The occurrence of hypertension is around 65% and preeclampsia up to 38% [3, 4]. Severe fetal growth restriction is seen in 50% of cases. In the first year post kidney transplant, pregnancy should be avoided due to the time needed to stabilize the graft function and doses of immunosuppressant medications [5]. Usually after one year post-transplant prophylaxis is finished and doses of immunosuppressive drugs are reduced. Azathiopryne is a drug of choice during pregnancy. Prednisone and prednisolone can also be used as are in 90% inactivated by placental enzymes. Cyclosporine and tacrolimus are also allowed to be used. Contraindicated are mycophenolate mofetil and cyclophosphamide [6]. Most of the pregnancies (82%) that were conceived during treatment consist of two medications and only 9% on three medications. However, only 3% according to research, conceived on regime consists of azathiopryne, tacrolimus and prednisone [7]. This immunosuppressant regime was used for our patient when she conceived twins. A further issue which is very important is the influence of immunosuppressant therapy on the fetus and the newborn. Observational studies suggest that azathioprine is safe in pregnant women. However, there are rare reports of congenital malformations such as: hypospadias, polydactyly, atrial or ventricular septal defect. Notwithstanding, there is no clear pattern of congenital malformations [5, 8, 9]. Prednisone in high doses – above 40 mg/d, can cause fetal growth restriction and neurodevelopmental delay [10]. Some series show increased risk of cleft palate, but most of the data suggests no effects on the fetus [5, 11]. In our case, the patient received low doses of prednisone, which makes it very unlikely that it was connected with FGR, especially that growth restriction was seen only in one twin. The third drug administered in our case was tacrolimus, which according to data does not cause fetal malformations and most authors reported favourable pregnancy outcomes [5, 6, 12]. However, there are consistent data that tacrolimus therapy can be connected with preterm delivery and low birth weight [13-15]. Furthermore, hypertensive medications such as labetalol (β-blockers) can be a cause of low birth weight, but in the described case, labetalol was added to the therapy when severe FGR in twin 2 was already diagnosed. Furthermore, there are no data about the side effect of the immunosuppressant therapy on the outcome of the babies at 12 or 24 months. At 12 months, according to literature, 93.75% and at 24 months 95.2% of the babies had normal development. The mild neurological deviations (muscle tone disturbances in lower limbs and slightly reduced muscle tone in lower limbs) were noted at one year of age only in babies who were born very prematurely. Notwithstanding, the respective findings had improved at age two [16]. In our case, the FGR twin has some motor development delay, but it seems to be caused by the fact of severe growth restriction and severe prematurity rather than the therapy adopted, as the development of the twin’s brother is normal (Fig. 1). Therefore, we can assume that the factor with the most influence on the outcomes is not the fact of having an organ transplant but prematurity and growth restriction, which are caused by the complexity of the medical condition. Additionally, based on this case report, we can identify how important cooperation and multidisciplinary teamwork is, as obstetrics and neonatology are not separate branches of medicine but are a continuity of each other.

DISCLOSURE

The authors declare no conflict of interest.

REFERENCES