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.