The outcome of pregnancies in women with cystic fibrosis--single centre experience 1998-2011.

OBJECTIVE: To describe the maternal and fetal outcomes of pregnancies in women with cystic fibrosis. DESIGN: Retrospective study. SETTING: Single obstetric hospital and adult cystic fibrosis centre. METHODS: Retrospective case-note review of pregnant women with cystic fibrosis referred for antenatal care and delivery. MAIN OUTCOME MEASURES: Maternal and fetal outcomes, mode of delivery, lung function and pregnancy complications. RESULTS: Forty-eight pregnancies were studied in 41 women. There were two miscarriages, 44 singleton pregnancies and two sets of twins. All babies were liveborn and survived. The mean gestational age at delivery was 35.9 ± 3.3 weeks. There were no fetal abnormalities or terminations of pregnancy. The median birthweight centile was 31.9 (interquartile range 14.9-55.6). Twenty-five (52.1%) of the women had pancreatic insufficiency and 17 (35.4%) required insulin. There was a positive correlation between booking predicted forced expiratory volume in 1 second (FEV(1) ) and gestational age at delivery (P < 0.01). Women with FEV(1) ≤60% were more likely to deliver earlier and by caesarean section compared with women with FEV(1) >60% (35.0 ± 3.2 weeks versus 37.1 ± 3.0 weeks; P = 0.02 and 75.0% versus 25.0%; P = 0.01). Three of the seven women with an FEV(1) <40% died within 18 months of delivery. Four of the eight women with FEV(1) 40-50% died between 2 and 8 years after delivery. CONCLUSION: Pregnancy for women with cystic fibrosis is possible and results in favourable maternal and fetal outcomes, but the incidence of preterm delivery and caesarean section is increased. Women with pre-existing poor lung function should be counselled antenatally to ensure that they understand the implications of their shortened life-expectancy and parenthood.

Presence of the 'lemon' sign in fetuses with spina bifida at the 10-14-week scan.

In three cases of lumbosacral spina bifida diagnosed at 12, 13 and 14 weeks of gestation there was an associated lemon sign, or scalloping of the frontal bones, and in one case the fetal nuchal translucency was increased. In a multicenter ultrasound screening study at 10-14 weeks there were 61,972 singleton pregnancies including 29 cases of spina bifida, none of which was diagnosed at the routine first-trimester scan, but 28 of the 29 cases were detected by ultrasonography at 16-22 weeks; in one case the diagnosis was missed at the 20-week scan and the defect was identified at 32 weeks during a scan for localization of the placenta. The fetal nuchal translucency was above the 95th centile in only one of the cases (3.4%). It is possible that the majority of fetuses with spina bifida have a lemon sign in the first trimester, but the sensitivity of the 10-14-week scan in the diagnosis of spina bifida and the prevalence of the lemon sign at this gestation will only be established by further studies incorporating early systematic examination of the head and spine.

Cystic adenomatoid malformation of the lung: prenatal diagnosis and outcome.

During an 8-year period (1984-1992), we made the ultrasonographic diagnosis of cystic adenomatoid malformation (CAM) of the lung in 58 fetuses at 17-39 weeks' gestation. We reviewed the records of these fetuses and combined the data from 74 cases reported in the literature to determine the incidence of the different types of CAM, associated malformations, and outcome. The lesions were macrocystic in 78 (59 per cent) and microcystic in 54 (41 per cent) of the cases. CAM was left-sided in 51 per cent, right-sided in 35 per cent, and bilateral in 14 per cent of the fetuses. In 15 (11 per cent) of the fetuses there were additional malformations and 57 (43 per cent) were hydropic. The pregnancy was electively terminated in 44 (33 per cent) of the cases, including all those with bilateral CAM. There were six (5 per cent) intrauterine deaths, five in association with hydrops, and one with growth retardation and heart defect. Of the 82 (62 per cent) infants that were liveborn, 21 (26 per cent) died in the neonatal period, 15 before and six after surgery. Of the 61 survivors, 16 (26 per cent) did not require surgery. In the 88 cases where the pregnancy was not terminated, survival was better if the CAM was macrocystic (74 per cent versus 58 per cent for microcystic), if there was no hydrops (92 per cent versus 21 per cent for hydrops), and if the amniotic fluid volume was normal or decreased (82 per cent versus 53 per cent for polyhydramnios).

Fetal thyroid function.

Cordocentesis has permitted the study of fetal thyroid function. In normal pregnancy, fetal blood thyroid-stimulating hormone (TSH), thyroid hormones and thyroid-binding globulin increase with advancing gestation demonstrating functional maturation of the pituitary, thyroid and liver, respectively. The administration of thyroid-releasing hormone to the mother produces a rapid increase in fetal TSH from at least 25 weeks gestation. In hypoxemic growth-retarded fetuses, the concentrations of TSH are higher, and the concentrations of total and free thyroxine are lower than in appropriately grown fetuses. In anemic fetuses from red cell-isoimmunized pregnancies, serum TSH and thyroid hormone concentrations are increased. In some chromosomally abnormal fetuses, particularly those with trisomy 21, TSH is increased.

Serum prolactin concentration in normal and small for gestational age fetuses.

OBJECTIVES: To study fetal and maternal serum prolactin concentrations in appropriately-grown (AGA) fetuses and in small for gestational age (SGA) fetuses. DESIGN: A cross-sectional study of 27 AGA and 27 SGA fetuses undergoing cordocentesis for prenatal diagnosis or for determination of fetal karyotype and acid-base balance. Serum prolactin concentration was measured by radioimmunoassay. SETTING: Harris Birthright Research Centre for Fetal Medicine. RESULTS: In the AGA group, both fetal and maternal serum prolactin concentration increased significantly with gestation (P < 0.001 and P < 0.01, respectively). In the SGA group, the fetal concentration of prolactin was significantly higher (P < 0.05), but the maternal serum prolactin concentration was not different from that of the AGA group. CONCLUSIONS: The finding of prolactin in the fetal circulation suggests that the anterior lobe of the pituitary is functioning from at least 12 weeks gestation. The increased serum prolactin concentration in SGA fetuses may be the consequence of hypoglycemic stress on the pituitary or the relative immaturity of the inhibitory hypothalamic-pituitary pathways.

Outcome of breech delivery at term.

OBJECTIVE: To compare neonatal mortality and morbidity in term infants presenting by the breech and delivered vaginally or by caesarean section. DESIGN: Population based comparison of outcomes. Data derived from the St Mary's maternity information system. SETTING: North West Thames Regional Health Authority, 1988-90. SUBJECTS: 3447 singleton fetuses presenting by the breech at term. MAIN OUTCOME MEASURES: Intrapartum and neonatal mortality, low Apgar scores, intubation at birth, and admission to special care baby units. RESULTS: After the exclusion of babies with congenital anomalies the incidence of intrapartum and neonatal death associated with vaginal birth was 8/961 (0.83%) compared with 1/2486 (0.03%) in babies born by caesarean section (relative risk 20, 95% confidence interval 2.5 to 163). The numbers of low Apgar scores and neonatal intubation were doubled in babies born vaginally or by emergency caesarean section compared with those delivered by elective operation. CONCLUSIONS: The good neonatal outcome associated with elective caesarean delivery of the term breech fetus may influence the decision of women and their obstetricians about mode of delivery.

Fetal thyroid function.

Cordocentesis has permitted the study of fetal thyroid function in utero. In normal fetuses, fetal TSH, TBG, and thyroid hormone concentrations increase progressively throughout intrauterine life. Fetal TSH concentrations are always high compared to nonpregnant adult values. TBG concentrations reach adult levels at term. TT4 and FT4 concentrations reach adult levels at approximately 36 weeks gestation, but TT3 and FT3 are always below adult concentrations. There are no significant associations between fetal and maternal concentrations of TSH, TBG, or thyroid hormones. The maternal administration of TRH from at least 25 weeks gestation stimulates the fetal pituitary gland to produce TSH. The response is rapid, unrelated to gestational age, and much greater than that of the mother. These findings suggest that in intrauterine life there is independent and autonomous maturation of the pituitary, thyroid, and liver. The fetal pituitary is able to respond to the maternal administration of TRH and appears to be more sensitive than in the adult. In small-for-gestational-age fetuses, the concentrations of TSH are higher and the concentrations of TT4 and FT4 are lower than in appropriately grown fetuses. The degrees of elevation of TSH and fall in thyroid hormones are significantly related to the degree of fetal hypoxemia and acidemia, respectively. Although the low concentrations of thyroid hormones may have some beneficial effects by reducing oxygen requirements, they may adversely affect brain development.

Relations between the fetal circulation and pituitary-thyroid function.

OBJECTIVE: To study the relation between changes in the fetal thyroid hormone and thyroid stimulating hormone (TSH) concentrations and alterations in the fetal circulation as assessed by Doppler ultrasound. DESIGN: A cross-sectional study of small for gestational age (SGA) and red-cell isoimmunized fetuses undergoing cordocentesis and Doppler studies for the assessment and determination of fetal karyotype, acid-base balance and haemoglobin concentration. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College, London. SUBJECTS: 38 growth retarded and 38 red-cell isoimmunised fetuses. INTERVENTIONS: Cordocentesis. MAIN OUTCOME MEASURES: Serum TSH total and free thyroxine (T4, FT4) and total and free triiodothyronine (T3, FT3) concentrations; middle cerebral artery (MCAVm) and descending thoracic aorta (AoVm) mean blood velocities; fetal Po2 and haemoglobin concentration (Hb). RESULTS: Delta values (delta) calculated as the number of SDs from the respective normal mean for gestation were used to compare the results with those from a previous study of normal fetuses. Mean AoVm was increased in the isoimmunized fetuses (P less than 0.001) but decreased in the SGA fetuses (P less than 0.001). Mean MCAVm was increased in both groups (P less than 0.01; P less than 0.001). There were significant associations between the gestational age adjusted values for TSH and MCAVm (r = 0.23, P less than 0.05) and between T4, FT4 or FT3 and AoVm (r = 0.41, P less than 0.01; r = 0.50, P less than 0.01; r = 0.36, P less than 0.01 respectively). In addition, T4 and FT4 were associated with delta Po2 and delta Hb. CONCLUSION: In the hypoxaemic hypoxia of growth retardation and the anaemic hypoxia of rhesus disease there are significant associations between changes in fetal thyroid hormone concentrations and changes in fetal blood flow as assessed by Doppler. Irrespective of whether altered blood flow is the cause or effect of changes in thyroid hormone concentrations, the observed changes could have beneficial effects for fetal survival, in the presence of a hostile intrauterine environment.

Thyroid function in small for gestational age fetuses.

Thyroid function was studied in fetal blood samples obtained by funipuncture from 49 small for gestational age (SGA) fetuses at 21-38 weeks' gestation. Levels of TSH, thyroxine-binding globulin, thyroxine (T4), free T4, triiodothyronine (T3), and free T3 were compared with those from 62 appropriate for gestational age (AGA) fetuses. Levels of TSH were significantly higher and T4 and free T4 significantly lower in the SGA than in AGA fetuses. Furthermore, there were significant associations between the increase in TSH and decrease in free T4 and the degrees of fetal hypoxemia and acidemia, respectively.

Fetal thyroid-stimulating hormone response to maternal administration of thyrotropin-releasing hormone.

Thyroid-stimulating hormone was measured in fetal blood samples obtained by cordocentesis before and after blood transfusion in Rh-affected pregnancies at 25 to 37 weeks' gestation. In eight of 26 study subjects thyrotropin-releasing hormone was given to the mothers immediately after the pretransfusion samples were obtained. In this group the fetal thyroid-stimulating hormone concentrations in the posttransfusion samples were significantly higher than those before the transfusion.

Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus.

BACKGROUND: Data on human fetal thyroid function have largely been derived from histologic studies or studies of cord-blood samples obtained at hysterotomy or delivery. These data may not represent true normal values. Cordocentesis (ultrasound-guided blood sampling from the umbilical cord) is a technique that allows investigation of physiologic processes in fetuses not under stress. METHODS: We measured serum thyroid-stimulating hormone, total and free thyroxine (T4), total and free triiodothyronine (T3), and thyroxine-binding globulin in blood samples from 62 fetuses. The samples were obtained by cordocentesis (n = 58) or cardiocentesis (n = 4) at 12 to 37 weeks of gestation. Maternal serum samples were obtained immediately before fetal blood sampling. RESULTS: Fetal serum thyroid-stimulating hormone, thyroxine-binding globulin, and total and free T4 and T3 concentrations increased significantly with the length of gestation (P less than 0.001). The only significant association among these variables, independent of the length of gestation, was between thyroid-stimulating hormone and free T4 (P less than 0.0001). Maternal serum concentrations of these variables did not change during gestation, and there was no significant relation between fetal and maternal values. Most fetal serum concentrations of thyroid-stimulating hormone were higher, whereas most serum total and free T3 concentrations were lower than the respective values for normal adults. The fetal serum total T4, free T4, and thyroxine-binding globulin values reached the level of the mean adult values at approximately 36 weeks of gestation. CONCLUSIONS: The increases in fetal serum concentrations of thyroid-stimulating hormone, thyroxine-binding globulin, and total and free T4 and T3 during gestation reflect increasing maturation of the pituitary, thyroid, and liver. The finding of increasing fetal serum concentrations of thyroid-stimulating hormone in the presence of increasing thyroid hormone concentrations suggests that the sensitivity of the fetal pituitary gland to negative feedback is limited or is counterbalanced by increasing stimulation by thyrotropin-releasing hormone from the hypothalamus.

Choroid plexus cysts and chromosomal defects.

During a 4-year period, 83 pregnant women with fetal choroid plexus cysts were investigated in our unit. Abnormal karyotypes were found in 20 fetuses, including trisomy 18 (n = 16), trisomy 13 (n = 1), triploidy (n = 1) and translocation Down's syndrome (n = 2). All fetuses with chromosomal defects had structural malformations in addition to the choroid plexus cysts.

Thyroid function in anemic fetuses.

Thyroid function was studied in 75 fetal blood samples obtained by cordocentesis from red cell isoimmunized pregnancies at 18-37 weeks of gestation. Thyroid-stimulating hormone (TSH), and free and total thyroxine and triiodothyronine were significantly higher than in normal controls. Furthermore, there was a significant association between the increase in TSH and the degree of fetal anemia.