Partial hydatidiform mole in a phenylketonuria patient treated with sapropterin dihydrochloride

Strict control of hyperphenylalaninemia is necessary in pregnant women with phenylketonuria (PKU) in order to prevent phenylalanine embryopathy in the fetus, characterized by intrauterine growth restriction, dysmorphic facies, congenital heart disease, microcephaly and intellectual disability, collectively known as maternal PKU syndrome. Sapropterin dihydrochloride (SD), an alternative or adjunct to dietary therapy in patients with tetrahydrobiopterin (BH₄)-responsive PKU, has recently been used in several cases to treat PKU during pregnancy with satisfactory results. Here, we report two pregnancies treated with SD and unrestricted diet in a patient with BH₄-responsive mild PKU. The first pregnancy resulted in a partial hydatidiform mole and was terminated, whereas a healthy infant was born from the second pregnancy. Phenylalanine control was optimal in both pregnancies. To the best of our knowledge, this is the first report on the development of partial hydatidiform mole associated with SD treatment and the second report on molar pregnancy in PKU. While the relation between SD and molar pregnancy is unknown, further studies may be needed to investigate the possible effects of SD on fertilization.     

Prenatal treatment of thyrotoxicosis to prevent intrauterine growth retardation

A woman with hypothyroidism and Graves ophthalmopathy was treated with propylthiouracil during her second pregnancy. This was employed because her first pregnancy resulted in an infant with severe intrauterine growth retardation and neonatal thyrotoxicosis. The antithyroid drug used during the second pregnancy crossed the placenta and treated the infant in utero. The infant was delivered by elective cesarean section at 36 weeks and was a live-born male with appropriate height and weight without evidence of thyrotoxicosis. The therapeutic benefit of propylthiouracil during this second pregnancy seems likely, based on the development of neonatal thyrotoxicosis after 4 days of life and on the presence of high thyroid-stimulating immunoglobulin levels in the mother and the infant.     

AGA-primed uteri compared with SGA-primed uteri and the success of subsequent in utero fetal programming

OBJECTIVE: To assess whether risk for early mortality is increased with recurrent small for gestational age (SGA) compared with nonrecurrent SGA. METHODS: We used the Missouri maternally linked cohort data containing births from 1978-1997. We identified mothers according to four categories: 1) appropriate for gestational age (AGA)-AGA: both first and second pregnancies were AGA; 2) AGA-SGA: first pregnancy was AGA, second pregnancy outcome changed to SGA (a switch); 3) SGA-AGA: first pregnancy was SGA, second pregnancy outcome AGA (a switch); 4) SGA-SGA: both first and second pregnancies were SGA. We then compared the success of fetal programming in the second pregnancy with a switch compared with a pregnancy without a switch (AGA-SGA compared with SGA-SGA; and SGA-AGA compared with AGA-AGA). We used neonatal mortality as primary outcome with infant and postneonatal mortality as secondary outcomes. RESULTS: Appropriate for gestational age infants from a SGA-primed uterus (SGA-AGA switch) had a 19% (odds ratio 1.19; 95% confidence interval 1.11-1.28) and 29% (odds ratio 1.29; 95% confidence interval 1.17-1.42) greater likelihood of infant and neonatal mortality, respectively, when compared with AGA infants from AGA-primed uterus (AGA-AGA; nonswitch). Approximately the same magnitude of risk elevation for neonatal and infant mortality was noted among SGA infants resulting from AGA-primed uterus (a switch) as among SGA infants from SGA-primed uterus (a nonswitch). Overall, the greatest risk of neonatal, infant, and postneonatal mortality was associated with an AGA-SGA switch. CONCLUSION: Fetal programming switch in subsequent gestation adversely affects early survival of affected infants compared with those with no change in fetal growth pattern.     

Successful pregnancy after renal transplantation in a patient with a urinary diversion.

A successful pregnancy is reported in a patient following renal transplantation and urinary diversion. The second half of pregnancy was complicated by hypertension, impaired renal function and obstruction of the ureter in the 35th wk. The latter complication required early termination of pregnancy by cesarean section. A healthy infant was delivered who survived without complications. Maternal renal function returned to pre-pregnancy levels following delivery.     

Nutrient intake and congenital heart defects in maternal phenylketonuria

OBJECTIVE: The purpose of this study was to determine whether nutritional components other than high maternal blood phenylalanine levels (> or = 10 mg/dL) are associated with congenital heart defects in the offspring of women with hyperphenylalaninemia. STUDY DESIGN: Of the 414 subjects who had live births, 249 women (60.1%) started diet treatment before 8 weeks of gestation and had nutritional assessments and infant outcome data. Maternal phenylalanine levels, protein intake, and the incidence of congenital heart defects were determined. Simple contingency table analysis was done by chi(2) and Fisher exact test. RESULTS: A significantly increased incidence of congenital heart defects was observed in offspring of mothers with hyperphenylalaninemia who had an elevated blood phenylalanine level >10 mg/dL at 0 to 8 weeks of gestation and a protein intake of < or = 50% of the recommended dietary allowance (P <.0013). CONCLUSION: An inadequate intake of protein during pregnancy in conjunction with elevated blood phenylalanine levels appear to have an additive effect in the incidence of congenital heart defects in the offspring of women with hyperphenylalaninemia.     

Maternal weight characteristics influence recurrence of fetal macrosomia in women with normal glucose tolerance

This study examines the relationship between maternal weight characteristics and recurrence of macrosomia in 111 non-diabetic women who delivered a second baby following primiparous delivery of a macrosomic infant (> 4500 g). Recurrence of fetal macrosomia was associated with greater maternal body mass index (P = 0.032), greater initial pregnancy weight (P < 0.05) and total weight gain during second pregnancy (P < 0.01). Women delivering a first macrosomic infant should avoid excessive weight gain before and during a subsequent pregnancy.     

Growth of the ultrasound fetal femur length during normal pregnancy: Part I

The growth of the ultrasound fetal femur length during normal pregnancy is presented. A total of 1,016 measurements of the fetal fernur length from 14 weeks' gestation through term were taken. The growth of the fetal fernur deacribes an asymptotic curve similar to the growth of the biparietal diameter with comparable limits of 2 SD. From the serial measurements performed, the growth rate of the femur has also been calculated. This begins at 3.15 mm/wk and slowly decreases to 1.55 mm/wk toward 40 weeks' gestation. Femur measurements provide the first repreducible determinations of “length” of the fetus to be measured by ultrasound throughout pregnancy.     

Discordant anencephalus in a Pergonal-induced triplet pregnancy

A patient with a triplet pregnancy had one infant affected by anencephalus. This pregnancy resulted from ovulation stimulation by gonadotropins. Several cases of association between anencephalus and induction of ovulation by clomiphene have been reported. The association with gonadotropins, however, has been reported only once. The event was prenatally diagnosed by ultrasound studies in the first and second trimesters. The association of anencephalus with ovulation stimulation is discussed briefly.     

Computer-assisted model of weight gain during pregnancy]

The goal of this study was to modelize the evolution of "ideal" weight gain during pregnancy and to generate automatically the appropriate diet. This computerized model has been developed on a microcomputer and has two units: the first unit calculates the "ideal" weight gain during pregnancy, based on the curves of Rosso which show that weight gain is not linear with term and depends of the prepregnancy weight. The second unit calculates the appropriate diet which is depending for the first visit on height, prepregnancy weight and weight gain and for the followed visits on weight gain and the diet situation of the previous visit. The next step will be the medical evaluation of this computer-aided modelization of weight gain during pregnancy.     

Vaginal delivery of monoamniotic twins with umbilical cord entanglement. A case report

BACKGROUND: Monoamniotic twinning is frequently complicated by umbilical cord entanglement and fetal death. Should vaginal delivery take place, this may present as an acute intrapartum emergency. CASE: A 26-year-old woman, gravida 3, para 2, presented in the second stage of labor and gave birth to a macerated, stillborn infant weighing 1,340 g. At the time of delivery it was not known that this was a twin pregnancy. Delivery was achieved only after division of a cord around the neck; it turned out to be that of a live, second twin. This infant, weighing 2,530 g, was delivered by rapid breech extraction and made a satisfactory recovery. CONCLUSION: When multiple pregnancy or monoamniotic multiple pregnancy has not been excluded, a nuchal cord might be that of an undiagnosed second twin.     

Abnormal fetal movements, micrognathia and pulmonary hypoplasia: a case report. Abnormal fetal movements

Background

Maternal weight and maternal weight gain during pregnancy exert a significant influence on infant birth weight and the incidence of macrosomia. Fetal macrosomia is associated with an increase in both adverse obstetric and neonatal outcome, and also confers a future risk of childhood obesity. Studies have shown that a low glycaemic diet is associated with lower birth weights, however these studies have been small and not randomised [1, 2]. Fetal macrosomia recurs in a second pregnancy in one third of women, and maternal weight influences this recurrence risk [3].

Methods/Design

We propose a randomised control trial of low glycaemic index carbohydrate diet vs. no dietary intervention in the prevention of recurrence of fetal macrosomia. Secundigravid women whose first baby was macrosomic, defined as a birth weight greater than 4000 g will be recruited at their first antenatal visit. Patients will be randomised into two arms, a control arm which will receive no dietary intervention and a diet arm which will be commenced on a low glycaemic index diet. The primary outcome measure will be the mean birth weight centiles and ponderal indices in each group.

Discussion

Altering the source of maternal dietary carbohydrate may prove to be valuable in the management of pregnancies where there has been a history of fetal macrosomia. Fetal macrosomia recurs in a second pregnancy in one third of women. This randomised control trial will investigate whether or not a low glycaemic index diet can affect this recurrence risk.

Current Controlled Trials Registration Number

ISRCTN54392969     

Is small for gestational age a marker of future fetal survival in utero?

OBJECTIVE: We sought to assess whether small for gestational age is a risk factor for stillbirth of a subsequent sibling. METHODS: The Missouri maternally linked cohort data set, containing data on births from 1978 through 1997, was used. We identified the study group (women who delivered a SGA infant in the first pregnancy) and a comparison group (women who delivered a non-SGA infant in their first pregnancy) and compared the outcome (stillbirth) in the second pregnancy between both groups. RESULTS: We analyzed information on the first and second pregnancies of 402,015 women (43,549 [10.8%] in the study arm and 358,466 [89.2%] in the comparison arm). Of the 1,883 cases of stillbirth in the second pregnancy, 314 cases occurred in mothers with a history of SGA (stillbirth rate 7.2/1,000) and 1,569 in the comparison group (stillbirth rate 4.4/1,000), P < .001. The adjusted risk of stillbirth was 60% higher in women with a prior SGA (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.4-1.8). The risk for stillbirth in the second pregnancy increased with decreasing gestational age at birth of the SGA infant in the first pregnancy (term: OR 1.4, 95% CI 1.2-1.6; preterm: OR 2.8, 95% CI 2.0-3.8; and very preterm: OR 4.2, 95% CI 2.4-7.3), P for trend < .001. CONCLUSION: Small for gestational age is a marker for subsequent stillbirth, and the risk rises with decreasing gestational age of the SGA birth. This information is potentially useful for counseling parents of SGA infants. LEVEL OF EVIDENCE: II-2.     

Paclitaxel and Platinum Chemotherapy for Ovarian Carcinoma during Pregnancy

BACKGROUND: Ovarian cancer diagnosed during pregnancy is uncommon. Paclitaxel-based chemotherapy during pregnancy has not been reported previously. CASE: A woman with ascites and an adnexal mass diagnosed during pregnancy at 27 weeks gestational age underwent a laparotomy with cytoreductive surgery and was diagnosed with stage IIIC papillary serous ovarian adenocarcinoma. She was treated with three cycles of paclitaxel and cisplatin during pregnancy. At 37 weeks, she underwent a cesarean section, abdominal hysterectomy, and cytoreduction. Three additional cycles of chemotherapy were given. She developed a recurrence within 6 weeks of completing chemotherapy. She received several cycles of chemotherapy, but died of recurrent cancer 29 months after diagnosis. The infant has normal growth and development at 30 months of age. CONCLUSION: This is the first reported case of paclitaxel use during pregnancy.     

The effect of posture on the blood pressure in pregnancy

Two studies of blood pressure with posture in pregnancy are reported. The first is a study of 20 normal primigravidae who remained normotensive throughout pregnancy. Arm and leg systolic and diastolic blood pressure and pulse rate were recorded in left lateral, supine and right lateral positions at 30 wk gestation and again 6–10 wk postpartum. There was no significant change in heart rate. The only fall occurred in the leg systolic blood pressure when the women lay supine in pregnancy. Otherwise the blood pressure invariably rose slightly as the women were turned from left lateral to supine to right lateral positions. These changes are explained by the hydrostatic difference between the level of measurement and the heart. The fall in leg systolic pressure when supine in pregnancy is attributed to vena caval compression.The second study was an evaluation of the ‘roll over’ test in predicting which pregnancies might develop preeclampsia. 85 primigravidae were tested at about 30 wk. There was no difference between the group who remained normotensive and those developing late pregnancy hypertension.     

Endodermal sinus tumor diagnosed in pregnancy: a case report

Pure endodermal sinus tumor (EST) of the ovary is an uncommon germ cell tumor characterized by rapid growth. Its occurrence during pregnancy is extremely rare. The case of a 34-year-old woman with EST stage IC diagnosed in the 22nd week of gestation is presented. She received four cycles of cisplatin monotherapy during pregnancy. Further, three cycles of combination chemotherapy (cisplatin, bleomycin, and etoposide) were administered. Twenty-eight months posttreatment the patient was in complete remission with good health. A healthy female infant was delivered by cesarean section in the 35th week of pregnancy. The child showed normal laboratory, pediatric, and neurologic examination at the time of discharge from hospital and during the first and second years of her life. We conclude that the prognosis of EST is very good if patient receives adjuvant therapy. Cisplatin monotherapy seems to be effective and safe during pregnancy.     

Hairy cell leukemia in pregnancy

Pregnancy complicated by HCL is an extremlely rare event: only 5 report of HCL in pregnancy have been previously described. A 36-year-old women was diagnosed of HCL presented in 14 week of her 5th pregnancy. Therapy was initiated in 18 wk of gestation with IFN-alpha at dose 6 x 106 U subcutaneous 3 times per week and prednisone 20 mg/d. IFN-alpha administration was well tolerated. After IFN-alpha therapy partial remission was achieved. The course of the pregnancy was normal. At week 39 of gestation a cesarean cection was performed and the patient delivered a healthy male infant weighing 3460 g with Apgar score of 10. The placenta was of normal size, no infiltration of hairy cell was founded. Post-partum course was uncomplicated. The patient elected to not breast feed her infant. 3 weeks after delivery patient had a 5-days course of 2CDA     

Complete chorioamniotic membrane separation with fetal restrictive dermopathy in two consecutive pregnancies

OBJECTIVE: To describe an instance of complete chorion-amnion membrane separation with fetal restrictive dermopathy in two consecutive pregnancies. METHODS: We performed prenatal ultrasounds in two consecutive pregnancies and evaluated gross and microscopic postnatal findings. RESULTS: The first pregnancy ended at 32 weeks of gestation with spontaneous chorioamniotic membrane separation and preterm premature rupture of membranes. The mother delivered an abnormal male infant with generalized fixed joint contractures, rigid and shiny skin, skin laceration around the neck, a rounded and opened mouth, and palpebral conjunctival eversion. The subsequent pregnancy was also complicated by spontaneous complete chorioamniotic membrane separation, oligohydramnios, and fetal growth restriction at 26 + 3 weeks of gestation. A immaturely born second baby also carried multiple anomalies similar to those of the first. Both infants died shortly after birth. After microscopic examination of the skin, we diagnosed the infant as restrictive dermopathy. CONCLUSIONS: Complete separation of the chorion-amnion membrane may be regarded as a serious prenatal condition. Restrictive dermopathy or skin disorders caused by defects in collagen or elastic tissue metabolism may be one of the many causes of chorion-amnion separation.     

Consecutive pregnancies in a menopausal woman following oocyte donation.

A second pregnancy was successfully achieved by a menopausal women who had previously conceived and delivered an infant using donated oocytes. The same nonanonymous oocyte donor provided the gametes for both procedures. Prior to embryo transfer, the functionally agonadal recipient received exogenous steroid hormone replacement therapy. Both pregnancies followed the transfer of 5 embryos which were conceived by the in vitro fertilization of the donated oocytes with the recipient husband's sperm. The first pregnancy ended with an intrauterine fetal demise at 40 weeks gestation. The second pregnancy is proceeding unremarkably.     

Modifiable risk factors for growth restriction in twin pregnancies

OBJECTIVE: This study was undertaken to evaluate modifiable risk factors for adverse fetal growth in twin pregnancies. STUDY DESIGN: A large cohort study from a database of women with twin gestations identified at risk for preterm labor was performed. Examining each infant's birth weight and gestational age at delivery, infants were classified as being average (AGA), large (LGA), or small (SGA) for gestational age, using the Alexander reference curve. Clinical and demographic factors were compared between patients delivering at least 1 SGA infant and AGA pairs using Pearson's chi2 Student t test statistics and logistic regression. RESULTS: There were 11,827 twin pregnancies evaluated. Risk factors associated with SGA deliveries included tobacco abuse, poor weight gain, lean prepregnancy body mass index, African American race, and nonmarried. The logistic regression identified tobacco abuse as the single greatest risk for poor fetal growth, (odds ratio [OR] 1.95; 95% CI [1.68, 2.27]). Weight gain of less than one-half lb/wk also increased SGA risk (OR 1.35; 95% CI [1.16, 1.68]), whereas weight gain greater than 1 lb/wk decreased SGA risk (OR 0.77; 95% CI [0.68, 0.86]). CONCLUSION: Tobacco abuse and weight gain are the modifiable risk factors, which require intervention during a twin pregnancy. Patients should be encouraged to stop tobacco abuse and gain a minimum of one-half lb/wk in the later half of pregnancy to minimize the risk for growth restriction.     

ANTI-HYPERTENSIVE DRUGS IN PREGNANCY AND FETAL GROWTH: EVIDENCE FOR “PHARMACOLOGICAL PROGRAMMING” IN THE FIRST TRIMESTER?

Objectives: To determine the timing and exact nature of the effect of the drug atenolol upon fetal growth. Also to discover if the reduction in fetal growth is due to superimposed pre-eclampsia or any other confounding variable. Design: A retrospective cohort study of prospectively collected data in a hypertensive pregnancy database. Setting: Two district general hospitals in the midlands of England. Both hospitals have specialised medical antenatal clinics for pregnant women with chronic hypertension. Participants: 491 pregnancies in 380 women with essential or secondary hypertension. Outcome measures: The outcome measures used were the infant birth weight, birth weight standardized for gestational age, and the ponderal index at birth, a surrogate measure for in utero growth restriction. Results: The babies of women taking atenolol at conception or during the first trimester had significantly lower birth weights (by 139–512 g, p<0.01) than women on calcium channel blockers or no medication. Likewise the ponderal index was also significantly reduced, p<0.01. In addition most of these babies were small for gestational age (SGA) with 70% on or below the 10th centile and 40% below the third centile. No such independent association was seen with anti-hypertensives taken in the second trimester. Conclusions: Atenolol taken at the time of conception and/or during the first trimester of pregnancy was associated with low birth weight. This finding was independent of the development of superimposed pre-eclampsia. Other anti-hypertensives were not found to be associated with low birth weight. Use of atenolol in the second trimester of pregnancy did not produce the same effect and was not materially different in its effects from the other anti-hypertensive drugs. In the second trimester, the development of superimposed pre-eclampsia is the over-riding effect in the reduction of infant birth weight. Atenolol used in the first trimester could be pharmacologically programming these infants to restricted growth patterns.