Case report
A Caucasian 26-year-old primigravida woman was referred to our gynecologic department at 12th gestational week on 2013. She was diagnosed with NF1when 5 months years old. Analysis of DNA-sequence has been performed when she was 11 years old with MLPA method without evidence of NF1 genetic mutations. The patient had no familial history positive for NF1 with healthy parents and one sister. She had a very low income, had a secondary upper school degree and was followed by social services due to poor social conditions. She had a history of smoke, but no alcohol or illicit drug use. Body mass index was 23. Menarche occurred at eleven years of age with normal menses. Psychological and physical development were normal. She underwent multiple surgeries to remove neurofibromas mainly located in skull bone, peritracheal tissue and next to the clavicle. Also, a palpebral neurofibroma was removed with poor esthetic result. MRI showed a 1 cm hyperdense lesion located at TH1 that was assumed to be an asymptomatic neurofibroma.
At the admission, patient was in good health with multiple evident café-au-lait patches over the skin, extensive freckling and diffuse neurofibromas in the skin, whose single maximal dimension was no more 2.5 cm in diameter. Obstetrical examination of external genitalia was normal with numerous small neurofibromas; vagina and uterine cervix appeared normal. Uterine volume corresponded to amenorrhea, with normal soft surface, no evidence of palpable mass in vagina, fornix or recto-vaginal septum. Blood pressure was normal. She did not show peripheral pitting edema. On physical examination a slight scoliosis was evident as well as a navel scar due to piercing. Heart and lung examination did not show anomalies and echocardiograph and abdominal ultrasound appeared normal. Patient refused ophthalmologic evaluation.
Fetal ultrasound showed a singleton fetus whose development was correspondent to amenorrhea (12th week). During genetic counseling the patient and her partner refused screening for fetal aneuploidies and prenatal diagnosis of NF1. A HIV-infection with low viral load( 200 copies/ml) and normal CD4+ cells count (568/mmc CD4+; CD4/CD8>1) was discovered during pregnancy evaluation at her first check-up at 12-week gestational age. Western-Blot confirmed HIV infection, but viral genotype was not performed due to the low viral loud. She was considered a HIV-elite controller and closely monitored by multidisciplinary medical team that included an expert in infectious disease. Moreover she denied risk behavior, except for a piercing performed one year before in an unsafe environment with a non-sterile needle.
A multidisciplinary team made by obstetric, infectious disease (ID) specialist, anesthesiologists and neonatologist discussed with the patient the possible effects of pregnancy on the disease and possible complications linked to NF1 and also risk for an HIV positive status for the fetus.
Since 19th week of pregnancy she was treated with Emtricitabine 200 mg/Tenofovir 245 mg a day (Truvada), Ritonavir 100 mg /day (Novir) and Atazanavir 300 mg/day (Reyataz). PCR-test showed absence of HIV-RNA after one month of therapy and 496/mmc CD4+ lymphocytes. She had no side effects due to antiretroviral therapy. The risk of low or no fetal infection during pregnancy was discussed with the couple. VDRL, TPHA, HCV, CMV, hepatitis A and B antibodies were negative. Pap test was normal and molecular test was negative for HPV infection. Vaginal culture was positive for mycoplasma infection that was successfully treated. Partner was negative for HIV and other common infection disease (HCV, hepatitis A and B, TPHA, VDRL, CMV). Doppler assessment of uterine artery was normal.
During second trimester cutaneous neurofibromas increase in numbers and dimension but none of them became relevant or giant. She then underwent routine fetal ultrasound and echocardiography that did not show any anomaly in growth or malformation. During routine anesthetic evaluation, there was no evidence of oral neurofibroma, she had adequate cervical mobility without palpable mass, and showed Mallampati 2. Near term of pregnancy lumbar MRI was suggested in order to evaluate TH1 lesions detected some years before and possible new occult neurofibroma that may have an effect on neuraxial anesthesia, if necessary, but she refused.
She spontaneously delivered a healthy female baby at 38-week gestational age without any perineal lesion. Zidovudine was promptly administered although undetectable viral load. Neonate had normal Apgar score and pH umbilical cord; she was HIV-RNA negative at birth and treated according to standard perinatal therapy with Zidovudine for 4 weeks. Lactation was inhibited. After delivery, patient continued to assume antiretroviral therapy, but refused any contraception. In the follow-up infant showed persistent negative HIV viral load.
During following years, patient had a miscarriage, and two other pregnancies. During each pregnancy she never showed increase in viral load, that remain undetectable, moreover CD4+ count was stable through years. Third pregnancy ended in spontaneous preterm delivery at 36 weeks with a healthy baby, normal Apgar score and ph In umbilical cord. There was no perineal lesion. Lactation was inhibited and the patient refused contraception.
During the forth pregnancy, the patient showed a steadily increase in CD4+ from 658/mmc to 900/mmc. She was admitted at 33-week of pregnancy in Emergency Department for massive uterine bleeding due to abruptio placentae and she underwent emergent caesarean section. Baby was low weight and showed low Apgar score at 1 and 5 minutes (6 and 8), but normal pH in umbilical artery. Lactation was inhibited and the patient refused again contraception.
In summary, the patient was compliant with HIV therapy without increase in viral load in the four pregnancy and she refused contraception. Moreover, even with adequate counseling she refused antenatal diagnosis for NF1 or prenatal screening for fetal aneuploidies. Babies were HIV-negative, during follow up, but two had clinical signs of NF1. Moreover neurofibromas remained stable and did not show any malignant degeneration.