Sex: F
Vaccine: HEPA, HPV4
Symptoms: Abdominal pain, Amenorrhoea, Breast tenderness, Dizziness, Drug exposure during pregnancy
Clinical narrative: Information has been received from a registered nurse, a Licensed Practical Nurse (LPN) and medical records for the Pregnancy Registry for GARDASIL, concerning a 17 year old female, gravida 1 Para 0, had chicken pox in the past, with no known drug allergies and with a history of depressive disorder of bipolar for which she was being treated with LEXAPRO (start date not reported) who on 17-AUG-2007 and 11-MAY-2009 was vaccinated with first dose (lot number 656051/0244U) and second dose (659184/0843X), respectively of GARDASIL, both doses were vaccinated in right deltoid IM. On 11-MAY-2009, the patient was also vaccinated with hepatitis A virus vaccine inactivated (MSD) (659832/0932) in left deltoid IM. Concomitant therapy included LEXAPRO and prenatal vitamin oral tablet 27-0.8mg, 1 tablet daily. On an unspecified date after the patient received the second dose of HPV vaccine, a PAP test was positive for HPV. On 16-SEP-2009, the patient presented with amenorrhea and positive home pregnancy test. The patient's LMP was on 01-JUN-2009 and the EDD was 08-MAR-2010. The father of baby (FOB). The patient had a paternal cousin with autism. FOB had a maternal uncle who was born with a diaphragm disorder and the "heart on the wrong side", the description was most suspicious for a congenital diaphragmatic hernia. It was also reported that the FOB's maternal great uncle had Down syndrome and with mental retardation. The patient's grandmother had breast cancer and her grandfather had diabetes and heart disease. After the patient discovered she was pregnant, she stopped taking LEXAPRO (stop date not reported). The patient had a body rash during her first trimester (no further details were provided). On 16-SEP-2009, her EGA was 15 weeks 2 days. Her cycles were regular and occurred approximately every 28 days. Her last pap smear, which was performed in 2007, showed normal, A urine pregnancy test was positive 3 weeks ago, which was on approximately 26-AUG-2009. Her last menstrual period was normal and lasted for 6 days. Since her LMP she had experienced nausea, abdominal pain, breast tenderness, fatigue, lightheadedness, vaginal discharge, urinary frequency and headache. She described the vaginal discharge as mucinous and white-colored. It had been present for 6 weeks. She denied vaginal bleeding and dysuria. Her past medical history was noncontributory. This was her first pregnancy. Since her LMP, she admitted to the use of tobacco. She had smoked less than 1 PPD since her LMP. She claimed her weight had not changed. In June and July, the patient experienced a rash with small red itchy bumps everywhere over entire body. BENADRYL cream was used and it resolved on an unspecified date. She felt it was related to mold in apartment since two other guys living in the apartment with them had the same symptoms, none since leaving. She denied fever. On 16-SEP-2009, the patient had an ultrasound performed to confirm gestational age. Ultrasound revealed a single fetus with positive heart rate of 157 BPM, femur length 15.4 millimeters, abdominal circumference (AC) 85.4 millimeters, head circumference (HC) 105.3 millimeters, biparietal diameter (BPD) 27.1 millimeters and the patient was at a gestational age of 14 weeks 6 days. Marked intracranial and thoraic abnormalities were noted and unable to visualize both lower extremities with only one foot was seen. The physician assessed suspected CNS abnormality of fetus and suspected fetal condition. The patient's papanicolaou (PAP) smear done on 16-SEP-2009 showed low grade squamous intraepithelial lesion (LGSIL) + human papillomavirus (HPV) high risk. On the same date, the following lab tests were ordered: Varicella antibodies, Toxoplasma antibody; IgG with reflex to IgM, Parvovirus antibody, Cytomegalovirus (CMV) antibody, thin layer pap with reflex to HPV; cervical/vaginal (ThinPrep or Surepath), QUAD test (AFP, HCG, Estriol, Inhibin A), obstetric panel, urine culture, Rubella antibody, Herpes Simplex, type 1 and type 2 antibody. On 17-SEP-2009, at a gestational age of 15 weeks 3 days, the patient had an ultrasound examination, whose indications was fetal assessment for malformation. Ultrasound revealed an active fetus with BPD 2.4cm compared with (c/w) 14 weeks 1 day (<5%), occipitofrontal diameter (OFD) 2.9cm, HC 9.0cm c/w 14 weeks 0 day (<5%), AC 8.8 cm c/w 14 weeks 4 day (45%), femur 1.6cm c/w 14 weeks 4 day 34%), humerus 1.7 c/w 14 weeks 6 day (39%), cephalic index 83 (71-87), HC/AC ratio 1.02 (1.05-1.39), biometry consistent with dates as previously established to within 8 days. Anatomy of the fetal thorax appeared within normal limits. The 4 chamber view appeared normal. The proximal left outflow was visualized. The proximal right outflow was visualized. The cardiac axis appeared normal. The interventricular septum appeared normal. The interatrial septum appeared normal. The abdominal cavity appeared normal. The fetal stomach appeared normal. Both kidneys appeared within normal limits. The fetal bladder appeared normal. The abdominal wall appeared intact. The spine was visualized from cervical to sacral region, within the resolution of the ultrasound equipment, without evidence of a neural tube defect. There was a misshapen skull with anterior and posterior bulging at the level of the forehead. Intracranial anatomy could not be well assessed at this early gestational age. The left foot appeared to be only partially presented. There were multiple fine amniotic bands noted in the amniotic fluid. Uterus and bilateral adnexes were within normal limits. All these findings were most consistent with an amniotic band syndrome, which may have its effect on the fetal skull and which may end up being lethal for this fetus. The physician had discussed this tentative diagnosis with the patient, and noted that this could also be a chromosomal abnormality or one of a number of syndromes, or it could be isolated anomalies. The physician discussed the potentially poor prognosis given the fetal skull/head findings at this time. The physician discussed amniocentesis to rule out a chromosomal abnormality, including 1/200-1/300 risk of a fetal loss from procedure. The patient had declined an amniocentesis for further evaluation on that day, but may consider it in the near future. On 18-SEP-2009, the patient was received the following laboratory tests: QUAD screen showed an elevated MSAFP of 4.51 NOM. Cystic fibrosis (CF) mutation screen was negative. TORCH titers showed HSV IgG and IgM positive (not distinguished between type 1 and type 2), which was suggestive of recent infection with either. On 08-OCT-2009, at gestational age of 18 weeks 3 days, the patient had an ultrasound examination, whose indication was fetal anomaly known or suspected. Ultrasound revealed an active fetus with AC 12.1 cm c/w 17 weeks 3 days (35%), femur 2.5cm c/w 17 weeks 4 day 25%), humerus 2.8 c/w 18 weeks 1 day (46%), biometry consistent with dates as previously established. Anatomy of the fetal thorax appeared within normal limits. The previous misshapen skull was again seen with anterior and posterior bulging at the level of the forehead. The right orbit did not appear to be developed or normally developed. Intracranial anatomy could not be well assessed and appeared disordered. The right leg was abnormally positioned. The right foot was abnormal and likely was missing a portion of the foot. The right hand remained clenched or might be missing some portions of the digits. There might be a ventricular septal defect (VSD), but difficult to confirm at this early gestational age. There were multiple fine amniotic bands again noted in the amniotic fluid. The patient selected to have amniocentesis done on that day and amniocentesis was performed by another physician under ultrasound guidance. On the first attempt 20 ml of clear fluid were obtained. The fluid was sent for Karyotype, AFP and FISH. The patient was Rh positive and globulin, immune (RHOGAM) was not administered. The amniotic fluid results revealed no evidence of numerical abnormality for chromosomes 13, 18, 21, X and Y. The karyotype was 46, XY, male karyotype. The patient's amniotic fluid AFP was 100.27 microgram/ml (10.78 MOM) (normal range: 18.80 microgram/ml (2.00 MOM)) and acetylcholinesterase was weak positive. The patient was recommended to return in 4 weeks (in early November) for fetal assessment including fetal echocardiography. On 28-OCT-2009, the patient, at gestational age of 21 weeks, presented for colposcopy for evaluation of a pap smear that revealed Bethesda LSIL. The patient was positive for HPV and HSV. The patient was positioned in the dorsal lithotomy position and a speculum was inserted into the vagina. The colposcopy was performed with and without 5% acetic acid staining of the cervix. The transformation zone was completely visualized. A cervical biopsy was not performed. An endocervical curettage was not performed. The procedure was notable for white epithelium, mosaic pattern and punctuation present diffusely. The physician assessed PAP smear of cervix with low grade squamos intraepithelial lesion (LGSIL) and cervical high risk human papillomavirus (HPV) DNA test positive. At the time of this report, the patient's outcome was unknown. Skull malformation and Amniotic Band Syndrome were considered congenital anomalies. The mother's experiences has been captured in WAES 0910USA00171. Additional information has been requested. All available medical records will be provided upon request.