Effect of monochorionicity on perinatal outcome and growth discordance in triplet pregnancy: collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. METHODS: This was a multicenter cohort study using population-based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000-2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth-weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. RESULTS: Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95% CI, 1.3-5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95% CI, 1.6-18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5-fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. CONCLUSIONS: Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence, antenatal management and perinatal outcome of monochorionic monoamniotic twin pregnancy: a collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancy and to describe perinatal outcome and clinical management of these pregnancies. METHODS: In this multicenter cohort study, the prevalence of MCMA twinning was estimated using population-based data on MCMA twin pregnancies, collected between 2000 and 2013 from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units. Pregnancy outcome at < 24 weeks' gestation, antenatal parameters and perinatal outcome (from ≥ 24 weeks to the first 28 days of age) were analyzed using combined data on pregnancies confirmed to be MCMA from NorSTAMP and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort for 2000-2013. RESULTS: The estimated total prevalence of MCMA twin pregnancies in the North of England region was 8.2 per 1000 twin pregnancies (59/7170), and the birth prevalence was 0.08 per 1000 pregnancies overall (singleton and multiple). Using combined data from NorSTAMP and STORK, the rate of fetal death (at < 24 weeks' gestation), including terminations of pregnancy and selective feticide, was 31.8% (54/170); the overall perinatal mortality rate was 14.7% (17/116), ranging from 69.2% at < 30 weeks to 4.5% at ≥ 33 weeks' gestation. MCMA twins that survived in utero beyond 24 weeks were delivered, usually by Cesarean section, at a median of 33 (interquartile range, 32-34) weeks of gestation. CONCLUSIONS: In MCMA twins surviving beyond 24 weeks of gestation, there was a higher survival rate compared with in previous decades, presumably due to early diagnosis, close surveillance and elective birth around 32-34 weeks of gestation. High perinatal mortality at early gestations was attributed mainly to extreme prematurity due to preterm spontaneous labor. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Sex and the pregnant kidney: does renal allograft gender influence gestational renal adaptation in renal transplant recipients?

BACKGROUND: Animal work indicates that ovarian hormones are important in initiating and maintaining enhanced renal function in pregnant rats and that a renal response resembling pregnancy can be provoked in male rats exposed to pregnancy hormones. Women becoming pregnant following renal transplantation provide an opportunity to compare the functional response of male and female allografts to the gestational endocrine environment. METHODS: This retrospective observational study included 20 renal allograft recipients (age 29.7 +/- 2.4 yrs) (mean +/- SE) who had 22 pregnancies beyond 24 weeks (gestation at delivery 35.5 +/- 0.6 weeks). Donor characteristics, transplant details, renal follow-up data, and information about pregnancy and allograft function were obtained from hospital notes. RESULTS: Thirteen women received male allografts (donor age 30.0 +/- 3.9 years) (mean +/- SEM) and 7 women, female allografts (donor age 45.1 +/- 6.0 years) (P = .04). There were no significant differences between the two groups in maternal recipient age, transplant to pregnancy interval, antenatal complications, pregnancy outcome, or postnatal graft function. Compared to prepregnancy values serum creatinine (SCr) decrements and augmented 24-hour creatinine clearance (CrCl) were observed over the first trimester in both male and female allografts: Delta CrCl from 106.8 +/- 13.2 mL/min to 114.4 +/- 11.4 mL/min (35.6% increase) and 71.8 +/- 7.4 to 89.5 +/- 11.3 mL/min (24.7% increase), respectively, and Delta SCr from 90.1 +/- 5.4 micromol/L to 73.6 +/- 6.6 micromol/L (17.8% decrease) and 99.8 +/- 9.7 micromol/L to 78.0 +/- 5.7 micromol/L (13.5% decrease), respectively. Differences between the two groups did not reach statistical significance. CONCLUSIONS: Donor gender and/or age do not appear to influence the gestational renal response in kidney transplant recipients.

Twin reversed arterial perfusion (TRAP) syndrome.

Twin reversed arterial perfusion (TRAP) syndrome is an extremely rare manifestation of feto-fetal transfusion syndrome. This condition is seen in monozygotic twin pregnancies, where the affected twin is perfused retrogradely by the healthy twin. The affected twin presents with bizarre malformations such as acardia and acephalus. We present such a case, which was diagnosed prenatally. The pregnancy progressed uneventfully to term.

Maternal uniparental heterodisomy for chromosome 2: detection through 'atypical' maternal AFP/hCG levels, with an update on a previous case.

We report a case of maternal uniparental disomy 2, detected through routine screening of placental karyotypes following the finding of 'atypical' AFP/hCG levels in the second trimester, with intrauterine growth retardation (IUGR) but otherwise normal outcome at term. Although the child remained small, subsequent early physical and mental development has also been normal. Additionally, we report long-term follow-up of an earlier case, again with relatively normal physical and mental development. The significance of atypical AFP/hCG results and the predictive value of prenatal testing for UPD2 in trisomy 2 confined placental mosaicism (CPM) cases are discussed.

Comparative trends in cause-specific fetal and neonatal mortality in twin and singleton births in the North of England, 1982-1994.

OBJECTIVE: To examine trends in cause- and birthweight-specific fetal and neonatal mortality rates in twins and singletons. DESIGN: Descriptive analysis based on a regional register. SETTING: The Northern Health Region of England, 1982-1994. SAMPLE: Two hundred and thirty-six fetal and 356 neonatal twin deaths; 2,687 fetal and 2,301 neonatal singleton deaths from a population of 10,734 twins and 505,477 singletons. MAIN OUTCOME MEASURES: Fetal and neonatal autopsy rates, cause- and birthweight-specific fetal and neonatal mortality rates in twins and singletons. RESULTS: The extended perinatal mortality (including stillbirths and neonatal deaths) rate (EPMR) was 55.2 per 1,000 in 1982-1994 in twins compared with 9.9 per 1,000 in singletons. The relative risk for twin compared with singleton deaths was 5.6 (95% CI 5.1-6. 1) being highest for immaturity (12.9, 95% CI 11.1-15.0). A significant decrease in the EPMR occurred in both twins and singletons in 1988-1994 compared with 1982-1987. The EPMR decreased mainly due to a reduction of deaths from antepartum asphyxia in twins and intrapartum asphyxia and trauma in singletons, as well as a reduction in congenital malformations in both groups. In both twins and singletons, birthweight-specific mortality rates improved between 1982-1987 and 1988-1994. CONCLUSION: The higher relative risk for twin deaths remained stable due to a similar decrease in the EPMR for both twins and singletons. The cause-specific relative risk in twins declined for antepartum asphyxia. The mortality rate resulting from lethal congenital malformations decreased in twins and singletons mainly due to earlier detection and subsequent termination of pregnancy.

Renal abnormalities on obstetric ultrasound as a presentation of DiGeorge syndrome.

We describe three pregnancies that presented with renal anomalies on obstetric ultrasound as the main abnormality and were subsequently found to have interstitial deletions within chromosome 22q11. A cardiac defect, double-outlet right ventricle, was also seen in the first case. Amnio infusion was refused in the second pregnancy and the perimembranous ventricular septal defect was not identified prior to termination. In the third case, there was no cardiac defect. The genitourinary abnormalities were a right hydroureter and hydronephrosis with a ureterocele bulging into the bladder lumen, bilateral multicystic kidneys with associated oligohydramnios, and a left multicystic kidney with right renal agenesis and associated oligohydramnios. Absence of thymus at autopsy in all three cases led to fluorescent in situ hybridization studies looking for the submicroscopic deletion of chromosome 22q11 associated with DiGeorge syndrome.

Maternal uniparental disomy for chromosome 2 in association with confined placental mosaicism for trisomy 2 and severe intrauterine growth retardation.

We report a liveborn infant with severe intrauterine growth retardation and renal failure, delivered following detection of non-mosaic trisomy 2 by chorionic villus biopsy in the first trimester. Detailed analysis post-delivery indicated apparent complete trisomy 2 of the chorionic tissues, with a chromosomally normal infant demonstrating maternal uniparental disomy for chromosome 2.

Fetal hepatic necrosis following blood sampling from the intrahepatic vein.

Previous reports have suggested that fetal blood sampling from the intrahepatic vein is not associated with significant fetal hepatic injury. We report a case of fetal liver necrosis occurring 24 h following blood sampling from the intrahepatic vein of a fetus with severe growth retardation at 34 weeks. The placenta was in a posterior position, precluding either blood sampling from the placental insertion or placental biopsy. Fetal death occurred in utero within 24 h of the procedure, which was carried out by an experienced operator. At post-mortem the liver appeared normally formed, but the right lobe was diffusely congested, with a well-defined demarcation line between the right and left lobes. Liver histology revealed extensive recent haemorrhagic necrosis of the right lobe.

Renal reserve during human pregnancy.

Pregnancy in healthy women is associated with increments in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). We hypothesized that the hyperfiltration of normal pregnancy attenuates or exhausts renal reserve. In 21 healthy females studied serially in early and late pregnancy and then on average 15 wk postpartum, GFR and ERPF were determined by inulin and p-aminohippurate clearances, respectively, before and during either an amino acid infusion (Vamin 9; Kabi Pharmacia) (n = 14) or a control infusion of Hartman's solution (n = 7), both infused at 4 ml/min for 210 min. In early and late pregnancy, GFR increased significantly in response to amino acid infusion [from 137 +/- 29 to 162 +/- 35 ml/min (P < 0.001) and from 134 +/- 29 to 148 +/- 40 ml/min (P < 0.01), respectively], with the increments (18 and 10%, respectively) not significantly different from postpartum (non-pregnant) when GFR increased by 12% from 94 +/- 22 to 105 +/- 23 ml/min (P < 0.002). Amino acid infusion significantly increased ERPF from 874 +/- 188 to 980 +/- 215 ml/min in early pregnancy (P < 0.01), from 684 +/- 135 to 773 +/- 181 ml/min in late pregnancy (P < 0.01), and from 507 +/- 121 to 560 +/- 141 ml/min postpartum (P < 0.006), increments of 12, 13, and 10%, respectively. GFR did not change in response to control infusion. We conclude that, despite gestational increments in renal hemodynamics of > 40%, pregnancy does not attenuate the renal response to amino acid infusion.

Effect of pregnancy on the long-term function of renal allografts: an update.

In 1992 we published a case-controlled study of posttransplant follow-up in 36 renal allograft recipients (Am J Kidney Dis 19:167-172, 1992). Eighteen of these patients became pregnant and comprise the index group; the 18 patients who did not become pregnant were considered controls. By the end of the follow-up period, plasma creatinine in the index group and controls had increased by 19% and 8%, respectively. Graft loss or chronic rejection occurred in one patient in the index group and in two in the control group. As there were no significant differences between the two groups, we concluded that pregnancy was unlikely to have a major effect on long-term graft function and/or survival. Subsequently, a case control study of Finnish women demonstrated graft survival favoring women who never conceived versus those who did (69% v 100%, respectively; P < 0.005) and thus prompted us to extend our posttransplant follow-up by a further 3 years. Data are currently available for 17 index subjects and 17 controls and during the entire follow-up period, graft losses have occurred in one index subject and in four controls. Plasma creatinine at the end of the follow-up period (1.40 +/- 0.52 mg/dL and 1.54 +/- 0.95 mg/dL, respectively) had increased from 3 years earlier by 11% and 7%, respectively, increments across time that were not significant. Although the increase in plasma creatinine was greater in the index subjects compared with the controls, there were no significant differences between the two groups. While our data do not exclude a minor deleterious effect of pregnancy on long-term graft function, we believe that female allograft recipients can be reassured that pregnancy is unlikely to substantially alter long-term graft function.

Renal haemodynamics and tubular function in human pregnancy.

In human pregnancy, effective renal plasma flow and glomerular filtration rate increase to levels 50-80% above non-pregnant values. The increments occur shortly after conception, persist throughout the second trimester and reduce slightly in late pregnancy. The hyperfiltration of pregnancy does not seem to be a potentially damaging process, as intraglomerular pressure remains unchanged. The increased excretion of glucose and other nutrients, as well as uric acid and protein, is related in part to altered tubular function. Renal physiology is altered so much in pregnancy that non-pregnant norms cannot be used in antenatal care.

Assessment of the renal circulation during pregnancy with color Doppler ultrasonography.

OBJECTIVES: A non-invasive method of assessing the renal vasculature during pregnancy would be useful in the management of patients with renal dysfunction resulting from preeclampsia or chronic renal disease. The objectives of this study were to determine (1) whether color ultrasonography during pregnancy facilitates Doppler interrogation of renal and intrarenal arteries, allowing (2) the assessment of differences between waveforms from nonpregnant and pregnant women and (3) the analysis of waveform variability throughout the kidney and between the right and left kidneys. STUDY DESIGN: In a cross-sectional study renal and intrarenal artery flow waveforms were obtained from women in early (12 to 19 weeks; n = 8), mid (20 to 29 weeks; n = 11), and late (30 to 37 weeks; n = 14) pregnancy with eight age-matched, nonpregnant women acting as controls. Waveforms were analyzed for pulsatility index, resistive index, and systolic/diastolic ratio. RESULTS: Left or right renal and upper- and lower-pole interlobar artery waveforms were obtained from all women. The mean pulsatility index values for the nonpregnant women were not significantly different from those women in early, mid, or late pregnancy. In the nonpregnant women, the left renal artery pulsatility index (1.13 +/- 0.13) was greater than the left lower interlobular artery pulsatility index (0.91 +/- 0.08; p < 0.05). During pregnancy renal and interlobar artery pulsatility index values were greater than those for the corresponding interlobular arteries, but the differences were not significant. Mean renal and intrarenal artery pulsatility index values were greater on the right, but the difference was significant only for the lower interlobular artery in midpregnancy. CONCLUSIONS: Pregnancy does not significantly affect renal and intrarenal artery flow waveforms, nor are there significant differences between waveforms from the renal and interlobar arteries.

Effect of pregnancy on long-term function of renal allografts.

Pregnancy in renal allograft recipients is associated with hyperfiltration with the potential for glomerular damage and adverse effects on long-term graft prognosis. We have undertaken a case-controlled study of posttransplant follow-up for a mean of 12 years (range, 4 to 23) in 36 female renal allograft recipients, 18 who became pregnant and 18 controls (matched to underlying disease and renal function) who did not. Assessments included plasma creatinine (PCr), glomerular filtration rate (GFR) by infusion clearance of inulin (Cin), mean arterial pressure (MAP), and documentation of antihypertensive therapy. By the end of follow-up, PCr in the pregnancy group (112 +/- 73 mumol/L [1.26 +/- 0.83 mg/dL]) and controls (127 +/- 52 mumol/L [1.44 +/- 0.59 mg/dL]) had increased by 19% and 8%, respectively, and GFR in the pregnancy group (58 +/- 29 mL/min) and controls (56 +/- 32 mL/min) had decreased by 18% and 7%, respectively. Graft loss or chronic rejection occurred in two patients in each group and there was a death in the pregnancy group 9 years after the second of two successful pregnancies. MAP in the pregnancy group (96 +/- 12 mm Hg) had decreased by 1%, and in the controls (101 +/- 9 mm Hg) had increased by 5%. Two patients in the index group and three in the control group commenced antihypertensive therapy during follow-up. There was, therefore, no evidence of an adverse effect of pregnancy in renal allograft recipients on long-term renal function or development of hypertension.

Perinatal outcome in renal allograft recipients: prognostic significance of hypertension and renal function before and during pregnancy.

With more renal allograft recipients becoming pregnant, it is important to refine existing pre-pregnancy assessment criteria and to identify other factors influencing perinatal outcome. We analyzed gestational renal response and acute or chronic hypertension in relation to perinatal outcome for 22 pregnancies that continued beyond 28 weeks' gestation in 17 allograft recipients (mean age 27 years, range 20-40) transplanted between 1967-1987. Before pregnancy, all had plasma creatinine of 1.62 mg/dL or less and 24-hour creatinine clearance of 39 mL/minute or greater. Six pregnancies were to four women on antihypertensive therapy. Mean arterial pressure (MAP), antihypertensive therapy, plasma creatinine, and 24-hour creatinine clearance were recorded before and during pregnancy. Perinatal outcome was adverse in ten pregnancies: five stillbirths, four growth-retarded infants, and one neonatal death, whereas 12 pregnancies had satisfactory perinatal outcome. Early-pregnancy increments and late-pregnancy decrements in renal function were identical in both groups. Mean arterial pressure was significantly higher at 16-28 weeks in women having adverse outcomes. Hypertension (MAP above 107 mmHg) occurred in 16 pregnancies (73%); it appeared before 28 weeks in seven and was invariably associated with adverse outcome. Hypertension appeared after 28 weeks in nine women and was associated with adverse outcome in only two cases. Five of six pregnancies in women who were on pre-pregnancy antihypertensive therapy ended in adverse outcome. It can be concluded that renal function was identical in pregnancies having adverse or satisfactory perinatal outcome, whereas hypertension before or during early pregnancy, albeit apparently satisfactorily controlled, appeared to be associated with adverse perinatal outcome.