R. Devlieger

Biochemical composition of fluids for amnioinfusion during fetoscopy.

Objective: To evaluate which of the commercially available solutions is best suited for amnioinfusion during fetoscopy, based on resemblance with the biochemical properties of amniotic fluid. Materials and Methods: Amniotic fluid samples from 10 pregnancies were studied. Specimens were obtained from 5 pathologic pregnancies (of which 3 were complicated by polyhydramnios) and 5 uncomplicated pregnancies. The concentrations of sodium, potassium, chloride, bicarbonate, calcium, glucose, osmolality, pH, total protein content and albumin were determined in each sample. A literature search (PubMed, Embase) was performed to identify commercially available fluids used for amnioinfusion in clinical practice. The composition of these infusion solutions was compared to the amniotic fluid samples mentioned above. Results: We identified two different electrolyte solutions used in clinical practice for amnioinfusion. We identified four additional commercially available solutions that could potentially be used for amnioinfusion. Most of these infusion solutions differ considerably from midtrimester amniotic fluid samples both in electrolyte composition and pH, with the most striking difference in the latter. Conclusion: Lactated Ringer’s solution approximates amniotic fluid the closest for both electrolyte composition and pH. This infusion solution seems to be the most suitable choice for amnioinfusion during fetoscopy.

Biochemical Composition of Amniotic Fluid in Pregnancies Complicated with Twin-Twin Transfusion Syndrome

Objective: To compare the electrolyte composition of pregnancies complicated with twin-twin transfusion syndrome (TTTS) with that of physiologic pregnancies. Materials and Methods: Amniotic fluid samples from 16 pregnancies were studied. Specimens were obtained from recipient sacs in 10 pregnancies undergoing fetoscopy for severe midtrimester TTTS. Additionally, 6 amniotic fluid samples were obtained transcervically from legal second-trimester pregnancy terminations. The concentrations of sodium, potassium, chloride, bicarbonate, calcium, glucose, osmolality, pH, total protein content and albumin were determined in each sample. Results: The mean gestational age at sampling was 20.2 weeks (range 17.2–27.1) in the TTTS group and 18.4 (range 16.0–22.0) in the control group (p = NS). We found significant lower levels of albumin (0.22 ± 0.04 vs. 0.39 ± 0.11, p = 0.01) and total protein (0.19 ± 0.08 vs. 0.51 ± 0.17, p < 0.001) and higher levels of bicarbonate (16.90 ± 1.45 vs. 14.50 ± 2.17, p = 0.02) in amniotic fluid samples taken from recipient sacs of TTTS pregnancies. Conclusion: Amniotic fluid from the receptor in severe midtrimester TTTS differs significantly from control amniotic fluid samples in bicarbonate concentration, total protein content and albumin concentration. These findings may help to understand the pathophysiology of TTTS and to optimise therapeutic modalities.

Mitogenic effect of insulin and developmental programming

To the Editor: We read with great interest the ‘For debate’article by Draznin in the February issue of Diabetologia onthe mitogenic effect of insulin as a possible causal factor forcancer [1]. This association is of great scientific interest andcould have a major impact on the clinical management ofthe many thousands of patients treated with insulin world-wide. Furthermore, this finding can be extended to theoccurrence of cancer within the framework of developmentalprogramming. Developmental programming is the process ofan insult in utero and/or in early postnatal life inducing apermanent response in the fetus and the newborn, leading toenhanced susceptibility to later diseases.In diabetic pregnancies, the insulin-producing beta cellsof the fetus are hyperactive, leading to hyperinsulinism andmacrosomia [2, 3]. Women who were macrosomic at birthhave an increased incidence of breast cancer in later life [4],and it has been postulated that hyperinsulinism during fetallife has a mitogenic effect on the developing breast [5].Moreover, studies have shown that fetal macrosomia isrelated to different tumours of the central and peripheralnervous system in later life [6, 7].We would like to underline the fact that the mitogeniceffect of insulin suggested by Draznin is indeed a problemduring fetal life, because high levels of insulin place thedeveloping organs under stress during critical periods ofdifferentiation.Thetreatmentofthediabeticpregnantwomanshouldfocus on preventinghyperinsulinism in the fetus. Thefetuses of mothers who are obese duringpregnancy are oftenobservedtohavehyperinsulinismandmacrosomia[8]. Sinceobesity is an important health problem, of even epidemicproportions, it is clear that efforts should be made to reduceobesity among women of reproductive age. This, as well asuniversal screening for, and adequate treatment of, diabetesduring pregnancy may help to reduce the risk of cancer inthe offspring by preventing fetal hyperinsulinism.

Effects of Epidural Clonidine and Neostigmine Following Intrathecal Labor Analgesia: A Randomized, Double-blind, Placebo-controlled Trial

Combined spinal-epidural (CSE) analgesia is often used to relieve the pain of labor, but the duration of the spinal component depends upon the spinal drug mixture and clinical factors such as parity, stage, and progression of labor. Only about 50% of women who receive a CSE late in the first stage of labor deliver within the period of time that the spinal component provides adequate analgesia. New combinations of analgesic drugs to prolong the duration of spinal analgesia are needed. This randomized, double-blind trial tested the hypotheses that spinal labor analgesia with a ropivacaine/sufentanil mixture can be prolonged by administering epidural clonidine and neostigmine and that epidural clonidine/neostigmine can reduce the local anesthetic administered during CSE. Seventy nulliparous women at term, with uncomplicated, singleton pregnancies presenting in the vertex position, were enrolled in the study. For the spinal component of the CSE, 0.175% ropivacaine 2.5mL with sufentanil 0.75 mg/mLwere injected intrathecally. If pain relief was adequate 15 minutes later, the study solution of either plain saline (P group) or 50mg neostigmine combined with 75 mg clonidine (NC group) was administered epidurally. Pain was assessed at 5, 10, 20, 30, 40, 50, and 60 minutes after the end of the spinal injection and every 60 minutes until delivery. The duration of initial analgesia was defined as the time between the end of the spinal injection and the first request for additional analgesia. Outcome measures were the duration of spinal analgesia, the total epidural local anesthetic consumption, and the number of patients who delivered without additional epidural analgesia. The 2 groups of 35 patients each were similar in demographic characteristics and baseline obstetric data. Obstetric outcomes were similar between the P and NC groups. The use of epidural clonidine and neostigmine prolonged the duration of initial spinal analgesia from 95 minutes [interquartile range (IQR), 70-120] in the P group to 144 minutes (IQR, 105-163) in the NC group (P<0.05). Nine patients in the NC group delivered before epidural analgesia was needed compared with 2 in the P group (P<0.05). Ropivacaine consumption was 12.7mg/h (IQR, 9.6-16.9) in the P group compared with 7.5mg/h (IQR, 3.011.9) in the NC patients. Pain scores were lower in the NC group compared with the NC group from 40 minutes until 120 minutes after initiation of analgesia (P<0.05). The rate of maternal hypotension after spinal analgesia and administration of study medication was similar between the two groups.Maternalmean blood pressure and heart rate did not differ between the groups nor were nausea and pruritus rates different. New onset of fetal heart rate changes did not differ between the groups and no differences in neonatal outcomes were found. Use of epidural clonidine and neostigmine can prolong the duration of the initial spinal analgesia during a CSE technique for labor but larger trials are needed to assess the safety of these drugs in obstetric patients.

P251: Does size matter? A randomised experimental comparison of 23 G versus 22 G needle for ultrasound guided invasive fetal procedures

The authors describe experiences gained over the period of 1984 and 1999 at two medical centers with chorionic villus sampling (CVS). Altogether 1149 CVSs had been performed between the 10th and 32nd gestational week. Prior to 1993 the transcervical approach (TC-CVS), after 1994 the transabdominal method (TACVS) was used. Analysis of data collected within the framework of this study was based on the following factors: indications for sampling, complications and incidence of pregnancy loss. 91.6% of the CVSs was carried out for the purposes of cytogenetic examination of the fetus. Over the past few years an increasing number of procedures had been carried out for molecular-genetic tests (7.6% of the total number of cases). Although the primary indication for cytogenetic tests was the advanced age of the mother, a remarkable increase in the number of samplings had taken place for the purpose of examining ‘‘suspicious ultrasound findings’’, minor anomalies detected by ultrasound. In this group the proportion of pathological cases was significantly higher (14%) than in all the other samplings, carried out for other indications. This data in itself underlines the importance of ultrasound-screening performed in the 18–20th weeks of gestation. Over the first half of the period being reviewed (1984–1993, TC-CVS), a fetal loss of 4.8% occurring within three weeks from the date of sampling, dropped to 1.7% in the period subsequent to year 1994 (TA-CVS). In cases of TA-CVS, both the complications and spontaneous abortions were less. In 74.1% of the cases, birth had taken place after the 37th week of gestation. Premature births (6.4%) and still birth-rate (1.1%) did not exceed normal rates observed in the general population. On the basis of our results, it is safe to say that in prenatal diagnosis, TA-CVS is a real alternative method of mid-trimester amniocentesis and it is recommended for use at any stage of the pregnancy.

Biochemical Differentiation of Gestational Compartments in the Midgestational Fetal Rabbit

Objectives: The fetal rabbit at midgestation is increasingly being used as a model in fetal diagnosis and therapy. In this study, we aimed to establish a reliable method for identification of the origin of sampled extra-embryonic fluids based on selected biochemical components. Methods: In 6 pregnant does at 22 days of gestation, 18 gestational sacs were sampled for amniotic, allantoic and exocoelomic fluid. These fluids, as well as matching maternal and fetal blood samples, were assayed for levels of sodium, potassium, chloride, bicarbonate, total protein, alkaline phosphatase, γ-glutamyl transferase and progesterone. Results: Levels of sodium and potassium were, respectively, lower and higher in the allantoic fluid when compared to other extra-embryonic spaces. Amniotic fluid had a significantly lower total protein content and higher level of alkaline phosphatase when compared to the exocoelomic fluid. Significant levels of progesterone could only be detected in maternal blood. Conclusions: In the midgestational rabbit, a combined assay of potassium, alkaline phosphatase and progesterone can determine the gestational cavity of origin of the sampled fluid. The obtained gradients for these markers suggest compartment-specific production and/or inter-cavity transfer mechanisms.

Contents Vol. 66, 2008

M.A. Belfort, Provo, Utah J. Bornstein, Nahariya H.L. Brown, Durham, N.C. C. Chapron, Paris P.G. Crosignani, Milan J. de Haan, Maastricht G.A. Dekker, Adelaide J.A. Deprest, Leuven K. Hecher, Hamburg S. Kahhale, São Paulo H. Kliman, New Haven, Conn. T.F. Kruger, Tygerberg J.A. Kuller, Raleigh, N.C. M.J. Kupferminc, Tel Aviv H. Minkoff , Brooklyn, N.Y. J. Moodley, Congella J.M. Mwenda, Nairobi H. Odendaal, Tygerberg J.T. Repke, Hershey, Pa. G.R. Saade, Galveston, Tex. Founded 1895 as ‘Monatsschrift für Geburtshilfe und Gynäkologie’, continued 1946–1969 as ‘Gynaecologia’ and 1970–1977 as ‘Gynecologic Investigation’

P06.08: TTTS before the limits of fetoscopic surgery

Results: 1037 were referred from January 1999 to May 2004. 189 patients (18.2%) had non-TTTS. Of these, 78 (41.2%) were iOLIGO, 65 (34.4%) iPOLY, and 46 (24.3%) sAFVd. Complete follow-up data was available in 141/189 (74.5%) patients. Progression to TTTS occurred in 37%, 26%, and 3% of iOLIGO, iPOLY and sAFVd groups, respectively (p < 0.001). iOLIGO patients were more likely to progress to IUGR than iPOLY patients (p < 0.04). Altogether, iOLIGO patients were less likely to remain unchanged (6.5%) than iPOLY (47.8%) or sAFVd (54%) (p < 0.001). Spontaneous normalization of AFV occurred in 6.5%, 2.2% and 54% of iOLIGO, iPOLY and sAFVd patients, respectively (p < 0.001). The average time for the development of TTTS in non-TTTS patients was 6.5 days. Conclusion: Monochorionic twins with AFV discordance may progress to TTTS or IUGR in a significant proportion of cases. Of the non-TTTS groups, iOLIGO patients are more likely to progress to a TTTS-IUGR. Ultrasound examinations weekly for AFV assessment and monthly for fetal growth are indicated in non-TTTS patients.

OC085a: Selective fetocide in monochorionic twins: Oral communication abstracts

differences were found in blood pressure, stiffness, in endothelium dependent and independent vasodilatation between the two groups. Conclusions: IUGR caused by placental insufficiency appears to be associated with impaired vascular growth persisting into young adulthood. The smaller aortic dimensions and higher resting heart rate seen in both males and females of the IUGR group and the lower aortic compliance coefficient seen in male adolescents may influence the future cardiovascular health in these individuals.

P343b: 50 consecutive cord coagulations in monochorionic twins

(MC) has a longer latency compared to singleton or dichorionic (DC) twin pregnancies with AEDF. Methods: All patients with AEDF in the UA were identified by search of the patient databases in 2 fetal medicine centres. After excluding 21 pregnancies due to incomplete data (n = 18), and structural or chromosomal anomalies (n = 3), a total of 53 MC pregnancies were compared with two cohort groups – singleton pregnancies (n = 74) and dichorionic twins (n = 19). Latency was defined as days from diagnosis of AEDF till delivery or intrauterine death. Results: A total of 146 pregnancies with AEDF were analysed, including 25 MC twins with IUGR (17%) and 28 with TTTS (19%). Median latency was 43 days (7–153) in the MC group, 30 days (1–66) in the DC group and 10 days (range 0–68) in the singletons. MC twins had significantly longer latency than the singletons (p = 0.007), but there was no significant difference with the DCDA. After excluding the TTTS group, non-TTTS MC twins had a significantly longer latency than DC twins. The overall median gestational age at onset of AEDF [176 days (range: 108–253)] was significantly earlier in MC twins (median 147 days) than in DC (190 days) or singleton (189.50 days) pregnancies (p < 0.001). Latency was linearly correlated with gestational age at onset of AEDF (R2 = 0.564). Conclusion: The latency of AEDF is longer in MC twins, suggesting a different patho-physiological mechanism then simple downstream resistance.