Francesca Anna Letizia Strigini

Serum thyrotropin by ultrasensitive immunoradiometric assay and serum free thyroid hormones in pregnancy

Variations of serum TSH, measured by an ultrasensitive immunoradiometric assay, of serum total and free thyroid hormones and of thyroxine-binding globulin (TBG) and sex hormone-binding globulin (SHBG) were investigated in a group of 18 normal women before and during pregnancy. A gradual increase of total thyroid hormones, TBG and SHBG was observed, while mean serum free thyroxine and free triiodothyronine progressively decreased. Serum TSH concentrations were comprised within the normal range throughout pregnancy, although a small but significant increase was found in the 2nd and 3rd trimester. These changes may represent a compensatory mechanism to meet the increased demand for thyroid hormones in pregnancy and must be taken into account for a correct evaluation of thyroid function during gestation.

Compensatory Feto-Placental Upregulation of the Nitric Oxide System during Fetal Growth Restriction

Background Fetal Growth Restriction is often associated with a feto-placental vascular dysfunction conceivably involving endothelial cells. Our study aimed to verify this pathogenic role for feto-placental endothelial cells and, coincidentally, demonstrate any abnormality in the nitric oxide system. Methods Prenatal assessment of feto-placental vascular function was combined with measurement of nitric oxide (in the form of S-nitrosohemoglobin) and its nitrite byproduct, and of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Umbilical vein endothelial cells were also harvested to determine their gene profile. The study comprised term pregnancies with normal (n = 40) or small-for-gestational-age (n = 20) newborns, small-for-gestational-age preterm pregnancies (n = 15), and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12). Results Umbilical blood nitrite (p<0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Fetal growth restriction umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Elevation in blood nitrite and S-nitrosohemoglobin persisted postnatally in the fetal growth restriction offspring. Conclusion Fetal growth restriction is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptative event to sustain placental blood flow. However, its occurrence may modify the endothelial phenotype and may ultimately represent an element of risk for cardiovascular disease in adult life.

Prenatal diagnosis of periventricular hemorrhage by fetal brain magnetic resonance imaging

Abstract Following the incidental diagnosis of triventricular hydrocephalus in a fetus 34 weeks after the mothers last menstrual period, during an uneventful pregnancy, 1.5-T brain magnetic resonance (MR) was carried out. A subependymal hemorrhage, which had not been revealed by transabdominal ultrasound, was found; this finding was confirmed by neonatal brain ultrasound and MR. Fetal MR allowed identification of the hemorrhage as the cause of the hydro-cephalus and also established its time of occurrence. Unexplained hydrocephalus should be included among the indications for fetal MR.

Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study

Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal complications.

Prenatal ultrasound and magnetic resonance imaging features in a fetus with Walker-Warburg syndrome

A 27-year-old woman was referred for targeted ultrasound examination at 26 weeks’ gestation following sonographic detection of fetal ventriculomegaly and posterior fossa abnormality. She and the father were Macedonian, non-consanguineous, healthy and had two healthy daughters. A mid-trimester abnormality scan had not been performed. On ultrasound examination the fetal cerebral ventricles were found to be enlarged (atrial width, 14 mm), the cerebellar vermis was not depicted and the fourth ventricle communicated with the cisterna magna, which was not enlarged (Figure 1). A median anechoic structure was interposed between the lateral ventricles, suggestive of a vein of Galen aneurysmal malformation. However, this diagnosis was easily excluded because the structure showed no signal on color Doppler imaging. Two days later, magnetic resonance imaging (MRI) confirmed the sonographic findings. Moreover, it showed a kinked Z-shaped brainstem, with bifid pons and medulla oblongata (Figure 2), and the mantle was thin with a simplified gyral pattern. The association of lissencephaly with cerebellar and brainstem anomalies suggested the diagnosis of Walker–Warburg syndrome (WWS). WWS is a rare autosomal recessive disorder characterized by congenital muscle dystrophy (CMD) and complex brain and eye abnormalities1,2. Additional ultrasound and MRI examinations showed progressive enlargement of the cerebral ventricles, the median anechoic structure and the cisterna magna (Figure 1c). At 31 weeks, retinal nonattachment/detachment and asymmetry of the eye globes were observed (Figure 3). At 41 weeks a male fetus was vaginally delivered, with a birth weight of 3400 g and head circumference of 37.5 cm. The neonate showed spontaneous respiratory activity, but was deeply hypotonic and required gavage nutrition for impaired swallowing. Postnatal MRI showed active hydrocephalus (necessitating ventriculoperitoneal shunt placement), the typical ‘cobblestone’ appearance of lissencephaly and abnormal cerebellar gyration (Figure 4). Muscular biopsy on day 15 showed severely increased variability of the diameter of muscle fibers and endomisial fibrosis together with immunohistochemical reduction of glycosylated alpha-dystroglycan2. Molecular analysis showed a homozygous mutation in the protein-Omannosyltransferase 1 (POMT1) gene (c.1611C>G, p.Ser537Arg), which has previously been detected in other cases of WWS3,4. The infant died at 6 months of age. In fetuses postnatally proven to be affected by WWS, the cerebral anomalies detected by prenatal sonography are usually non-specific5 and suggestive of WWS only in cases with a positive family history. When familial history is uninformative, only the association of cerebral or cerebellar with ocular anomalies can suggest the correct diagnosis6,7. In the current case, sonography showed ventriculomegaly and dysplastic cerebellum, and the diagnosis of WWS was suspected after the detection of lissencephaly, bifid pons and medulla oblongata and kinked brainstem by MRI8,9. The ocular abnormalities, which confirmed the diagnosis6,7,9, were only observed 1 month later. Late-onset microphthalmia and late diagnosis of retinal detachment have been described previously5,10. Aside from the findings that were used to diagnose WWS, listed above, the most peculiar sonographic finding at presentation was the midline oblong anechoic structure. This feature was explained when MRI showed separation of the bifid portions of the brainstem, together with its downward displacement (Figure 2).

Modifications in uterine and intraovarian artery impedance in cycles of treatment with exogenous gonadotropins: effects of luteal phase support.

OBJECTIVE To determine the effects of induction of multiple ovulation and of luteal P supplementation on the impedance to blood flow in the uterine and intraovarian arteries during the luteal phase. DESIGN A prospective study using transvaginal color flow Doppler imaging. SETTING A university-based infertility center. PATIENTS Fifty-six women with unexplained or male factor-related infertility undergoing IUI. INTERVENTIONS The patients were studied either during spontaneous cycles (n = 16) or in cycles of induction of multiple follicular development with purified FSH (n = 40). In 18 treated cycles, the luteal phase was supplemented with natural P. MAIN OUTCOME MEASURES The pulsatility index was recorded from uterine and intraovarian arteries on the day of E2 peak and 5 and 10 days thereafter. On the same days, E2 and P plasma levels were measured by RIA. RESULTS The intraovarian pulsatility index was significantly lower in FSH-treated than in spontaneous cycles on the day of E2 peak. Also, the uterine pulsatility index was significantly lower in treated cycles than in spontaneous cycles on the day of E2 peak and 5 days thereafter. In the late luteal phase, P supplementation was correlated with a significant decrease in uterine pulsatility index as compared with both spontaneous cycles and FSH-treated cycles without luteal support. CONCLUSIONS Multiple follicular development is associated with a significant reduction in the impedance to perifollicular blood flow. Progesterone, as well as E2, seems able to decrease the impedance to blood flow in uterine arteries in women.

Systemic vasculitis and pregnancy: A multicenter study on maternal and neonatal outcome of 65 prospectively followed pregnancies

OBJECTIVE Systemic vasculitis (SV) are uncommon diseases that rarely affect women during their reproductive age; little data, mainly retrospective, is available on this topic. The aim of our study was to evaluate maternal/neonatal outcome and disease course before, during and after pregnancy. METHODS Sixty-five pregnancies in 50 women with SV were followed by a multispecialistic team in 8 institutions between 1995 and 2014. Clinical data on pregnancy, 1year before and 1year after delivery was retrospectively collected. The rate of pregnancy complications was compared to that of a General Obstetric Population (GOP) of 3939 women. RESULTS In 2 patients the diagnosis of SV was done during pregnancy; 59 out of the remaining 63 started when maternal disease was quiescent. We recorded 56 deliveries with 59 live births, 8 miscarriages and 1 fetal death. In SV, preterm, particularly early preterm (<34weeks) deliveries and cesarean sections appeared significantly more frequent than in GOP (11.3% vs 5.0%, p=0.049 and 48.2% vs 31.0%, p=0.009). Vasculitis-related complications occurred in 23 pregnancies (35.4%), with 5 severe events (7.7%) including 3 cases of transient ischemic attack (TIA). Data about the post-partum period were available for 56 pregnancies: 12 flares (21.4%) occurred, with 1 severe event (1.8%). CONCLUSION SV patients can have successful pregnancies (especially during a disease remission phase) despite an increased rate of preterm delivery. Severe flares were limited, but the occurrence of 3 TIA suggests that particular attention should be given to possible thrombotic complications in SV patients during pregnancy and puerperium.

Outcome of pregnancy in Italian patients with primary sjogren syndrome

Objective. To investigate pregnancy and fetal outcomes in patients with primary Sjögren syndrome (pSS). Methods. An obstetric history of 36 women with established diagnosis of pSS at pregnancy was obtained from a multicenter cohort of 1075 patients. In a subgroup case-control analysis, 12 deliveries in patients with pSS were compared with 96 control deliveries. Results. Thirty-six women (31 with anti-SSA/Ro and/or anti-SSB/La antibodies) with an established diagnosis of pSS had 45 pregnancies with the delivery of 40 newborns. Two miscarriages, 2 fetal deaths, and 1 induced abortion were recorded. Mean age at the first pregnancy was 33.9 years; mean number of pregnancies was 1.25; 18/40 (45%) cesarean births were delivered; mean pregnancy length was 38.5 weeks (range 32–43), with 6 preterm deliveries. The mean Apgar score at 5 min was 8.9, mean birthweight was 2920 g (range 826–4060 g). Congenital heart block (CHB) occurred in 2/40 (5%) newborns. The reported rate of breastfeeding for at least 1 month was 60.5%. In 4/40 pregnancies (10%) a flare of disease activity was observed within a year from delivery. In the case-control subgroup analysis, 12 deliveries were compared with 96 controls and no significant differences were found. Conclusion. Patients with pSS can have successful pregnancies, which might be followed by a mild relapse. CHB was the only cause of death for offspring of mothers with pSS.

Prolactin-Releasing Action of a Low Dose of Exogenous Gonadotropin-Releasing Hormone Throughout the Human Menstrual Cycle

Pharmacological doses of gonadotropin-releasing hormone (GnRH) are known to induce prolactin (PRL) release in different pathological states. The same effect can be observed in postmenopausal women and during the phases of menstrual cycle characterized by high estrogen levels. With the aim to evaluate whether nonpharmacological doses of GnRH are also able to induce PRL release, gonadotropin and PRL response to a low dose of GnRH (10 micrograms, i.v. bolus) was evaluated in 70 normal women during different phases of their menstrual cycle. A significant PRL increase was observed in 33% of subjects during the first days of the cycle (menstrual phase; days 1-3 from the beginning of menstrual bleeding: n = 6), in 24% of subjects during early follicular phase (days -10 to -8 from LH peak: n = 17); in 38% of subjects during midfollicular phase (days -6 to -4 from LH peak: n = 8); in 78% of subjects during preovulatory phase (days -2 to -1 from LH peak; n = 9); in 67% of subjects during postovulatory phase (days +1 to +2 from LH peak; n = 6) and in 42% of subjects during midluteal phase (days +5 to +8 from LH peak; n = 24). In brief, the increase of mean PRL levels after GnRH administration was only significant (p less than 0.05) during pre- and postovulatory phases. The percentage of patients who showed a PRL response during the different phases of menstrual cycle was significantly correlated to the mean maximal net increase of LH (r = 0.927; p less than 0.01) and to the mean maximal net increase of FSH (r = 0.926; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjusting the dose to the individual response of the patient during the induction of ovulation with pulsatile gonadotropin-releasing hormone

To identify the effective dose of intravenous pulsatile gonadotropin-releasing hormone necessary to induce ovulation in patients with chronic anovulation of diverse etiology, 40 women were subdivided into four groups: idiopathic hypogonadotropic hypogonadism (IHH), functional hypothalamic amenorrhea, normoandrogenic oligomenorrhea, and polycystic ovarian syndrome (PCOS). During 90 treatment cycles, the dose was the only parameter that was progressively adjusted. The overall ovulation rate per cycle was 100% in IHH, functional hypothalamic amenorrhea, and normoandrogenic oligomenorrhea, using only 5 micrograms/90 minutes in functional hypothalamic amenorrhea and normoandrogenic oligomenorrhea and up to 7.5 micrograms/90 minutes in IHH. In PCOS, the ovulation rate was 67.6%, using up to 20 micrograms/90 minutes. The lesser degree of effectiveness observed in PCOS can probably be explained by the different basal endocrine profile presented by these subjects.