Stuart Ward

Fetal Leptin Influences Birth Weight in Twins with Discordant Growth

The objective of this study was to determine the plasma leptin concentrations in twin pregnancies in relation to chorionicity and discordant fetal growth. We studied 53 twin pregnancies of which 26 had growth discordance of ≥20% and 27 were concordant for growth (discordance of ≤10%). Paired maternal and fetal blood samples were obtained at birth. Plasma leptin concentrations were measured by RIA. In discordant monochorionic pregnancies, fetal plasma leptin concentrations in the intrauterine growth-restricted twins were lower than the co-twins with normal growth (mean difference, 3 ng/mL; 95% CI, 2.2 to 3.3 ng/mL;p < 0.001), whereas no such differences were present between concordant monochorionic twin pairs (mean difference, 0.1 ng/mL; 95% CI, −0.2 to 0.5 ng/mL; NS). Similarly, fetal plasma leptin concentrations in appropriate-for-gestational-age twins were higher than in the intrauterine growth-restricted twins of the discordant dichorionic pregnancies (mean difference, 2.4 ng/mL; 95% CI, 1.8 to 3.1 ng/mL;p < 0.001). No such differences were present between the concordant dichorionic twin pairs (mean difference, 0.2 ng/mL; 95% CI, −0.1 to 0.5 ng/mL; NS). Maternal plasma leptin concentrations were comparable among all four groups and were higher than the fetal levels. Fetal plasma leptin concentrations of the intrauterine growth-restricted twins of discordant monochorionic and dichorionic pregnancies were comparable. There was a positive association between cord plasma leptin concentrations and the birth weight of twin pairs (y = 0.002 x − 0.32;r = 0.63;p < 0.001;n = 106). A significant positive association was also found between percent differences in birth weight and fetal delta plasma leptin concentrations of the discordant monochorionic and dichorionic twin pairs (y = 0.057 x + 0.93;r = 0.60;p < 0.001, n = 26). In conclusion, irrespective of chorionicity, plasma leptin concentrations in intrauterine growth-restricted twins were 2-fold lower than their co-twins with normal growth. These differences may be attributed to placental factors.

Discordant Amino Acid Profiles in Monochorionic Twins with Twin-Twin Transfusion Syndrome

To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n = 12) and without (n = 12) twin-twin transfusion syndrome (TTTS).In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids—valine (p < 0.001), leucine (p < 0.001), iso-leucine (p < 0.05), histidine (p < 0.001) and L-arginine (p < 0.001)—were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p < 0.001), serine (p < 0.01), glycine (p < 0.001) and tyrosine (p < 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 ± 64 versus 396 ± 23 μM;p < 0.001) and the non-TTTS twin pairs (p < 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism.

Influence of vasopressin in the pathogenesis of oligohydramnios-polyhydramnios in monochorionic twins.

OBJECTIVESnThe pathophysiology of oligohydramnios-polyhydramnios in monochorionic (MC) twins complicated by chronic twin-twin transfusion syndrome (TTTS) is poorly understood. We hypothesise that oliguria and oligohydramnios in the donor twin of chronic TTTS, occurs due to antidiuretic and vasoconstrictive activity of vasopressin (AVP).nnnMETHODSnWe measured AVP levels in maternal, fetal and amniotic fluid samples obtained in utero and at birth from 44 MC twins with (n=27) or without chronic TTTS (n=17). Concentrations of AVP in pg/ml were determined by immuno-radiometry assay.nnnRESULTSnIn donor fetuses, plasma and amniotic fluid AVP levels were higher than those of the recipient twins in utero (P<0.001) and at birth (P<0.001). No such differences were found between the non-TTTS twins. The plasma AVP concentrations were higher in the recipient fetuses with severe hydrops than those without hydrops (2.8+/-0.7 pg/ml versus 0.3+/-0.3 pg/ml; P<0.05). Maternal AVP levels were comparable between the TTTS and non-TTTS groups. In the non-TTTS twins, both plasma and amniotic fluid AVP levels were higher than those of the recipient twins (P<0.001) but lower than those of the donor twins (P<0.001). There was a significant association between amniotic fluid and plasma AVP levels both in the TTTS (r=0.78; P<0.001) and non-TTTS (r=0.70; P<0.01) infants.nnnCONCLUSIONSnVasopressin concentrations in the donor twins were three times higher than their co-twins which suggests that oligohydramnios may occur as a consequence of AVP mediated reduction in fetal urine output.

Perinatal outcome following amniotic septostomy in chronic TTTS is independent of placental angioarchitecture.

OBJECTIVES: To determine whether the vascular anatomy of monochorial placenta influences the success of amniotic septostomy for the treatment of chronic mid-trimester twin–twin transfusion syndrome, we report placental anastomoses and perinatal data of 13 pregnancies treated by amniotic septostomy in combination with amnioreduction (AR). The placental anastomoses were delineated postnatally by perfusion studies. Perinatal outcome was also evaluated in relation to umbilical artery Doppler waveform of the donor twin.RESULTS: The median gestational age at septostomy was 21 weeks (range 18 to 25.5 weeks). Amniotic septostomy in combination with single AR procedure successfully resolved polyhydramnios in all cases. The median gestational age at delivery and the septostomy to delivery interval were 27 weeks (range 20 to 34 weeks) and 4 weeks (range 0.3 to 13.6 weeks), respectively. Of the 26 fetuses, 10 died in utero and four died within a week of life, with a combined survival rate of 46%. There was no relation between the clinical outcome and angioarchitecture of the placenta. However, pregnancy loss was higher in the donor twin with absent end-diastolic flow umbilical artery Doppler waveform than those with end-diastolic flow (85 vs 17%; p<0.001).CONCLUSION: This study suggests that although amniotic septostomy is a promising method for the correction of oligohydramnios and/or polyhydramnios, perinatal survival rate does not depend on angioarchitecture of the placenta. Instead, umbilical artery Doppler waveform of the donor twin may be a better marker for survival rate.