Early vaginal progesterone versus placebo in twin pregnancies for the prevention of spontaneous preterm birth: a randomized, double-blind trial.

BACKGROUND: In women with a singleton pregnancy and sonographic short cervix in midgestation, vaginal administration of progesterone reduces the risk of early preterm birth and improves neonatal outcomes without any demonstrable deleterious effects on childhood neurodevelopment. In women with twin pregnancies, the rate of spontaneous early preterm birth is 10 times higher than that in singletons, and in this respect, all twins are at an increased risk of preterm birth. However, 6 trials in unselected twin pregnancies reported that vaginal administration of progesterone from midgestation had no significant effect on the incidence of early preterm birth. Such apparent lack of effectiveness of progesterone in twins may be due to inadequate dosage or treatment that is started too late in pregnancy. OBJECTIVE: The early vaginal progesterone for the prevention of spontaneous preterm birth in twins, a randomized, placebo-controlled, double-blind trial, was designed to test the hypothesis that among women with twin pregnancies, vaginal progesterone at a dose of 600 mg per day from 11 to 14 until 34 weeks' gestation, as compared with placebo, would result in a significant reduction in the incidence of spontaneous preterm birth between 24+0 and 33+6 weeks. STUDY DESIGN: The trial was conducted at 22 hospitals in England, Spain, Bulgaria, Italy, Belgium, and France. Women were randomly assigned in a 1:1 ratio to receive either progesterone or placebo, and in the random-sequence generation, there was stratification according to the participating center. The primary outcome was spontaneous birth between 24+0 and 33+6 weeks' gestation. Statistical analyses were performed on an intention-to-treat basis. Logistic regression analysis was used to determine the significance of difference in the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation between the progesterone and placebo groups, adjusting for the effect of participating center, chorionicity, parity, and method of conception. Prespecified tests of treatment interaction effects with chorionicity, parity, method of conception, compliance, and cervical length at recruitment were performed. A post hoc analysis using mixed-effects Cox regression was used for further exploration of the effect of progesterone on preterm birth. RESULTS: We recruited 1194 women between May 2017 and April 2019; 21 withdrew consent and 4 were lost to follow-up, which left 582 in the progesterone group and 587 in the placebo group. Adherence was good, with reported intake of ≥80% of the required number of capsules in 81.4% of the participants. After excluding births before 24 weeks and indicated deliveries before 34 weeks, spontaneous birth between 24+0 and 33+6 weeks occurred in 10.4% (56/541) of participants in the progesterone group and in 8.2% (44/538) in the placebo group (odds ratio in the progesterone group, adjusting for the effect of participating center, chorionicity, parity, and method of conception, 1.35; 95% confidence interval, 0.88-2.05; P=.17). There was no evidence of interaction between the effects of treatment and chorionicity (P=.28), parity (P=.35), method of conception (P=.56), and adherence (P=.34); however, there was weak evidence of an interaction with cervical length (P=.08) suggestive of harm to those with a cervical length of ≥30 mm (odds ratio, 1.61; 95% confidence interval, 1.01-2.59) and potential benefit for those with a cervical length of <30 mm (odds ratio, 0.56; 95% confidence interval, 0.20-1.60). There was no evidence of difference between the 2 treatment groups for stillbirth or neonatal death, neonatal complications, neonatal therapy, and poor fetal growth. In the progesterone group, 1.4% (8/582) of women and 1.9% (22/1164) of fetuses experienced at least 1 serious adverse event; the respective numbers for the placebo group were 1.2% (7/587) and 3.2% (37/1174) (P=.80 and P=.06, respectively). In the post hoc time-to-event analysis, miscarriage or spontaneous preterm birth between randomization and 31+6 weeks' gestation was reduced in the progesterone group relative to the placebo group (hazard ratio, 0.23; 95% confidence interval, 0.08-0.69). CONCLUSION: In women with twin pregnancies, universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation. Post hoc time-to-event analysis led to the suggestion that progesterone may reduce the risk of spontaneous birth before 32 weeks' gestation in women with a cervical length of <30 mm, and it may increase the risk for those with a cervical length of ≥30 mm.

Management of red cell alloimmunized pregnancies using conventional methods compared with that of middle cerebral artery peak systolic velocity.

The aim of this retrospective study was to find out the effect of change in the management of red cell alloimmunized pregnancies from conventional method of amniocentesis to the Doppler assessment of middle cerebral artery peak systolic velocity (MCA-PSV). There were 29 alloimmunized pregnancies affected by red cell antibodies. Ten cases were managed by amniocentesis and another 19 were managed by MCA-PSV measurements. The antenatal management and perinatal outcome of both groups are presented. This study suggests that the non-invasive monitoring should be the method of choice to monitor alloimmunized pregnancies.

Third trimester intrauterine fetal death caused by arterial aneurysm of the umbilical cord.

Umbilical artery aneurysm (UAA) of the umbilical cord is an extremely rare lesion, with only 8 reported cases in the English-language literature; 7 of these were associated with significant fetal morbidity or mortality and 4 were associated with fetal trisomy 18. We report an additional case of UAA with normal karyotype that resulted in intrauterine growth restriction and fetal demise. It has been suggested that these aneurysms cause fetal hypoxia and intrauterine fetal death, either by compression of the umbilical vein or by acute kinking of the umbilical cord. Cytogenetic analysis should be performed in all cases diagnosed with this unusual lesion, and placental mosaicism for trisomy 18 should be excluded.

Agenesis of the ductus venosus associated with direct umbilical venous return into the heart--case series and review of literature.

OBJECTIVES: The purpose of our study was to review our own experience and the available literature on the prenatal diagnosis of absent ductus venosus associated with direct insertion of the umbilical vein into the heart. METHODS: A retrospective review of the database of a tertiary fetal cardiology centre. The literature was searched for cases with a prenatal diagnosis of such an umbilical venous anomaly. RESULTS: Between January 2000 and June 2003, nine fetuses were diagnosed as having absence of the ductus venosus with the umbilical vein directly draining into the heart. This represents the largest reported clinical experience of this anomaly. We also report, to our knowledge, the first prenatal diagnosis of insertion of the umbilical vein into the left atrium. Combining our series with those found in the literature, a total of 35 cases were identified. Cardiomegaly was reported in 25 of the 35 cases (71%). Structural cardiac abnormalities and other extra-cardiac anomalies were found in 13 of the 35 cases (37%). Hydrops was present or developed in 6 cases (17%). The outcome data were available for 33. The overall survival rate was 67% (22 of 33). CONCLUSIONS: Careful assessment of the ductus venosus and the umbilical vein should be a part of the evaluation of every fetus with unexplained cardiomegaly. All fetuses with abnormal connection of the umbilical vein should undergo a clinical and ultrasonographic assessment both in utero and after birth to exclude any cardiac and extra-cardiac abnormalities. During the prenatal period, serial ultrasound examinations are indicated and delivery is considered when there is evidence of progressive cardiovascular compromise.

Vacuum extraction: is there any need to improve the current training in the UK?

OBJECTIVE: The objective of this study was to assess the use and efficacy of delivery by vacuum extraction or ventouse in routine clinical practice and to assess some aspects of the procedure that may reflect the quality of training in this technique. MATERIALS AND METHODS: Women's demographic profiles and delivery details were collected in both the prospective (B) and retrospective (A) arm of the study. In addition, in the prospective arm of the study two custom-designed forms were used: the obstetrician recorded their perception of where the vacuum cup had been placed on one form while on a second form the pediatrician indicated the actual site of the cup placement as observed from the position of the chignon. All the diagrams of cup placement were reviewed by one of the authors, who was blinded to the outcome of the procedure. RESULTS: The vacuum extractor was the first instrument to be used in 79% and 87% of the instrumental deliveries in groups A and B, respectively, with corresponding failure rates of 20% and 21%. Although an occipito-posterior position was diagnosed in 11% of cases of group A and 14% of cases of group B, the specifically designed occipito-posterior cup was not used at all. The vacuum cup was considered to have been applied suboptimally in 40% of the cases where attempted vacuum delivery failed. CONCLUSION: The high rate of inappropriate positioning of the cup may reflect difficulty in accurately applying the cup, perhaps due to caput or malposition, but may also represent poor assessment of the orientation and position of the fetal skull and therefore be indicative of a need for improvement in training methods.

Monoamniotic twins: what should be the optimal antenatal management?

Monoamniotic twinning is a rare event with an incidence of 1% of all monozygotic twins and associated with a high fetal morbidity and mortality. Confident early diagnosis is possible, but optimal management is not yet established. This article presents the experience of a single centre in managing all monoamniotic twins diagnosed during 1994-2000. Seven pairs of monoamniotic twins were identified for analysis. All were managed in accord with a unit protocol that involved early diagnosis, serial ultrasound examination and elective early delivery. In four cases, the detection of monoamnionicity was made during a first trimester nuchal scan. Discordance for structural abnormality was found in three cases where the co-twin was normal. Cord entanglement was detected antenatally in four cases. Two pairs of twins died before 20 weeks. One of these had early onset twin-twin transfusion syndrome. In five cases, the pregnancy continued beyond 20 weeks. A live birth rate of 90% and intact survival of 70% were achieved in this group. We believe that ultrasound is reliable in diagnosing monoamniotic twins and the detection of cord entanglement. Timing of elective delivery is a balance between the risks of preterm birth at a specific gestational age in an individual centre compared with the unquantifiable risks of fetal death if an expectant policy were pursued. The decision to deliver and at which gestational age should combine input from the parents, neonatologist, fetal medicine consultant and the obstetrician.