Morbidity and development in childhood of infants born after temporising treatment of early onset pre-eclampsia.

OBJECTIVE: To assess morbidity and development in childhood of infants born after temporising management of severe early onset pre-eclampsia. DESIGN: Cohort study with matched controls. SETTING: University centre for high risk obstetrics. SAMPLES: Three groups of neonates matched for gender and year of birth: one born after temporising treatment of severe early onset (<32 weeks) pre-eclampsia with an average delay of delivery of two weeks (n= 193); one born at the duration of pregnancy [1 week] of the pre-eclamptic mother on admission (control group I, n = 192); and one born at the same gestational age [1 week] as the infant of the pre-eclamptic mother (control group II, n= 189). METHOD: Follow up at four years of age or more using medical records and questionnaires. MAIN OUTCOME MEASURES: The presence of various morbidities including mental retardation, cerebral palsy, motor skill problems, visual handicap, hearing loss, speech and language problems, education level and acute or chronic respiratory problems. RESULTS: Median follow up of seven years (range 4-12) was achieved in 159 infants in the study group (83%), 122 in control group I (64%) and 110 in control group II (58%). Missing data analysis showed no differences in neonatal characteristics and morbidity between infants with and without follow up in the study group. All major and minor handicaps were less frequent in the study group than in control group I but statistical significance was reached only for acute and chronic respiratory disorders in the study group (13.8%) compared with control group I (27%). CONCLUSION: Average delay of delivery of two weeks with temporising management in severe early onset pre-eclampsia is associated with a reduced risk of respiratory disorders in childhood.

Anal sphincter damage after vaginal delivery: functional outcome and risk factors for fecal incontinence.

OBJECTIVE: To assess the role of anal sphincter damage following delivery in the development of anorectal complaints and urinary incontinence, and to identify obstetric factors associated with subsequent fecal incontinence. METHODS: The retrospective cohort study with matched controls used a postal questionnaire and analysis of delivery and operation records from all women who underwent primary repair of a third or fourth degree perineal rupture in our hospital between 1971 and 1991, and their controls, matched for date and parity. Frequencies of complaints were compared using the Mantel-Haenszel common odds ratio [OR] for matched-control studies. Obstetric risk factors for fecal incontinence were assessed with multivariate logistic regression analysis. RESULTS: In the period studied, 171 women underwent a primary repair. One hundred and forty-seven of which returned the questionnaire (86%), compared with 131 of the controls (73%). Analysis was performed on 125 matched pairs with a median follow-up of 14 years. Fecal incontinence was reported by 39 patients and 16 controls (OR: 3.09; 95% confidence interval: 1.57-6.10). Urinary incontinence was reported by 65 cases and 52 controls (OR:1.46; 95% CI: 0.91-2.37). Among women with anal sphincter damage, the extent of anal sphincter damage was an independent risk factor for fecal incontinence. (OR: 2.54; 95% CI: 1.45-4.45). Subsequent vaginal delivery was not associated with the development of fecal incontinence (OR: 2.32; 95% CI: 0.85-6.33). In primiparous women mediolateral episiotomy protected for fecal incontinence after anal sphincter damage (OR: 0.17; 95% CI: 0.05-0.60). CONCLUSIONS: Anal sphincter damage following delivery is significantly associated with subsequent anorectal complaints, but not with urinary incontinence. The extent of sphincter damage is an independent risk factor for the development of fecal incontinence. Mediolateral episiotomy protects for fecal incontinence in primiparous women.

The Marfan syndrome and pregnancy: a retrospective study in a Dutch population.

OBJECTIVE: To assess the course and outcome of pregnancies in women with the Marfan syndrome with the aim of developing guidelines for counseling. STUDY DESIGN: A retrospective study based on data collected from members of the Dutch Association of Marfan patients. Pregnancies and neonatal outcomes of affected mothers were compared with those of non-affected mothers who delivered a Marfan infant. RESULTS: In a group of 44 affected women 78 pregnancies beyond 24 weeks of gestation were evaluated, compared with 51 in non-affected women. Obstetric course and neonatal outcome of pregnancy were similar in both groups. Aortic dissection was observed in five affected women, three of which were known to have an aorta diameter of 40 mm or more; two neurovascular events were recorded; all mothers survived. CONCLUSIONS: A preconceptional aortic diameter of 40 mm or more, progression of dilatation and decreased cardiac function are risk factors in pregnancy for women with the Marfan syndrome. A multidisciplinary approach is recommended for the care of these patients and their infants.

Release of tumor necrosis factor-alpha and prostanoids in whole blood cultures after in vivo exposure to low-dose aspirin.

BACKGROUND: The preventive effect of low-dose aspirin in cardiovascular disease is generally attributed to its antiplatelet action caused by differential inhibition of platelet cyclooxygenase-1. However, there is evidence that aspirin also affects release of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). It is not known whether this is caused by direct action on the cytokine pathway or indirectly through cyclooxygenase inhibition and altered prostanoid synthesis, or both. METHODS: We assessed the capacity of lipopolysaccharide-activated leukocytes in whole blood cultures of eight healthy subjects following a single oral dose of 80 mg aspirin to release TNF-alpha, prostanoid E2 (PGE2) and prostanoid I2 (PGI2), and thromboxane A2 (TXA2). TNF-alpha and prostanoids were determined by enzyme-linked immunoassays. RESULTS: In seven subjects, TNF-alpha release in blood cultures decreased 24h after intake of aspirin. The effect of aspirin on prostanoid release was assessed in three individuals: PGE2 increased in all subjects, PGI2 increased in two and remained unchanged in one, and TXA2 was reduced in two and unchanged in one individual The presence of DFU, a specific inhibitor of cyclooxygenase 2, did not affect the reduction of TNF-alpha release by aspirin, but abolished prostanoid production in all three individuals. CONCLUSION: The capacity of activated leukocytes to release TNF-alpha is reduced by ingestion of low-dose aspirin, independent of changes in prostanoid biosynthesis.

Risk factors for third degree perineal ruptures during delivery.

OBJECTIVE: To determine risk factors for the occurrence of third degree perineal tears during vaginal delivery. DESIGN: A population-based observational study. POPULATION: All 284,783 vaginal deliveries in 1994 and 1995 recorded in the Dutch National Obstetric Database were included in the study. METHODS: Third degree perineal rupture was defined as any rupture involving the anal sphincter muscles. Logistic regression analysis was used to assess risk factors. MAIN OUTCOME MEASURES: An overall rate of third degree perineal ruptures of 1.94% was found. High fetal birthweight, long duration of the second stage of delivery and primiparity were associated with an elevated risk of anal sphincter damage. Mediolateral episiotomy appeared to protect strongly against damage to the anal sphincter complex during delivery (OR: 0.21, 95% CI: 0.20-0.23). All types of assisted vaginal delivery were associated with third degree perineal ruptures, with forceps delivery (OR: 3.33, 95%-CI: 2.97-3.74) carrying the largest risk of all assisted vaginal deliveries. Use of forceps combined with other types of assisted vaginal delivery appeared to increase the risk even further. CONCLUSIONS: Mediolateral episiotomy protects strongly against the occurrence of third degree perineal ruptures and may thus serve as a primary method of prevention of faecal incontinence. Forceps delivery is a stronger risk factor for third degree perineal tears than vacuum extraction. If the obstetric situation permits use of either instrument, the vacuum extractor should be the instrument of choice with respect to the prevention of faecal incontinence.

Neonatal outcome of temporizing treatment in early-onset preeclampsia.

OBJECTIVE: To assess the effect of prolongation of pregnancy on neonatal outcome by means of hemodynamic treatment in patients with early-onset preeclampsia. STUDY DESIGN: A retrospective case-controlled study of 222 liveborn infants of patients with early-onset (24--31 weeks) preeclampsia, who underwent temporizing hemodynamic treatment. Of the two control groups of liveborn preterm infants of non-preeclamptic mothers one group was matched with the study group for gestational age on admission (group I), one for gestational age at birth (group II). Primary outcome measures were neonatal and infant mortality and variables of neonatal morbidity. RESULTS: Median gestation in the study group of preeclamptic patients was prolonged from 29.3 to 31.3 weeks. No difference in neonatal or infant mortality was observed between infants from preeclamptic mothers and in the control groups. The study population showed better results than control group I with regard to admission to NICU (P<0.01), mechanical ventilation (P<0.001) and intracranial hemorrhage (P<0.01). Control group II had better results than the study group with respect to birthweight (P<0.001), bronchopulmonary dysplasia (P<0.01), patent ductus arteriosus (P<0.01), and retinopathy (P<0.01). CONCLUSION: Prolongation of gestation in patients with early-onset preeclampsia may reduce neonatal morbidity, but neonates of the same gestational age without a preeclamptic mother still have a better prognosis.

Prevention of pre-eclampsia: status and perspectives 2000.

Because pre-eclampsia is a relatively common complication of pregnancy and forms a major cause of maternal, fetal, and neonatal morbidity and mortality, attempts at prevention are justified, but hampered by the fact that as yet no reliable and acceptable screening tests for women at risk are available. Analysis of the many interventions advocated to prevent or delay the onset of pre-eclampsia reveals that dietary calcium supplementation and prophylactic low-dose aspirin treatment have shown promise of efficacy in small randomized, placebo-controlled trials, but the results of large, multicenter trials are generally disappointing. The disappointing results obtained in large, multicenter trials may in part be explained by the lack of strict criteria for inclusion, late initiation of treatment, use of ill-defined end points, different timing of aspirin ingestion, and low patient compliance. Recent evidence that supplementation with vitamins C and E could prevent pre-eclampsia awaits confirmation. Future clinical trials on prevention of pre-eclampsia should be based on results of basic research.

Placental transfer of the thromboxane synthetase inhibitor ridogrel in the late-pregnant ewe.

OBJECTIVES: To assess the occurrence of placental transfer of the thromboxane synthetase inhibitor ridogrel in the pregnant ewe and to determine its effect on prostanoid levels in the ewe and fetal lamb, on uterine contractility and on maternal and fetal hemodynamics. STUDY DESIGN: Five chronically instrumented pregnant ewes at 122 days of gestation received intravenous infusions of 5 mg/kg/3 h ridogrel and solvent. Maternal and fetal arterial samples were obtained at predetermined intervals to determine concentrations of ridogrel and prostaglandin metabolites TXB2, 6-keto-PGF1alpha, PGF2alpha, and PGE2. Maternal and fetal responses of blood flow and pressures were determined. RESULTS: Fetal ridogrel levels were 25% of maternal concentrations. Ridogrel showed rapid and marked thromboxane synthetase inhibition and augmentation of levels of prostaglandin metabolites. There was no evidence of change in amniotic pressure, uterine blood flow, maternal and fetal blood pressure and heart rate. CONCLUSION: Ridogrel is a potent thromboxane synthetase inhibitor which passes the sheep placenta, does not influence maternal and fetal hemodynamics and uterine contractility, and shows similar antiplatelet activity in the ewe and the fetal lamb.

Prediction and prevention of pregnancy-induced hypertensive disorders.

Because hypertensive disorders complicating pregnancy are common and constitute a leading cause of maternal, fetal and neonatal morbidity and mortality, prevention attempts appear to be justified. Primary prevention is only possible by avoiding pregnancy. Secondary prevention requires identification of patients at risk. A large number of predictive methods have been published and the majority appear to be of no or limited value. At present only the determination of inactive urinary kallikrein and uteroplacental colour-pulsed Doppler velocimetry show promise and require further assessment. Analysis of the many interventions advocated for prevention of pre-eclampsia reveals that only dietary calcium supplementation and prophylactic low-dose aspirin have shown promise of efficacy in small controlled clinical trials, but the results of large, multicentre trials are disappointing. The disappointing results obtained in large, multicentre trials may be explained, at least in part, by the lack of strict eligibility criteria and end-points and by low patient compliance. Prophylactic low-dose aspirin is recommended in women at high risk because it is associated with a moderate reduction in risk, may reduce the severity of pre-eclampsia if it develops and appears to be safe for mother and infant. The present data do not support any prophylactic intervention in pregnant women at low or medium risk.

Fetal liver volume measurement by three-dimensional ultrasonography: a preliminary study.

OBJECTIVE: To establish the application of three-dimensional ultrasonography in measuring fetal liver volume during the second half of normal pregnancy. DESIGN: A prospective cross-sectional study of normal fetal liver volume at 19-39 weeks of gestation (median 29 weeks). SUBJECTS: Thirty-four non-smoking women with a singleton pregnancy resulting in the delivery of a healthy infant with a birth weight between the 5th and 95th centiles according to the Kloosterman tables adjusted for maternal parity and fetal sex. METHODS: For fetal liver volume measurements, a simultaneous recording of a frontal section of the liver immediately anterior to the stomach and a sagittal section of the liver were obtained using a standard Combison 530 ultrasound machine with a 5-MHz annular array transducer for volume scanning. RESULTS: Technically acceptable fetal liver volume measurements were obtained in 25 of 34 participating women. Mean fetal liver volume data (P50) ranged between 8 ml at 20 weeks' gestation and 116 ml at 38 weeks' gestation. A statistically significant increase in normal fetal liver volume was found with advancing gestational age (p < 0.0001) and with increasing estimated fetal weight (p < 0.00001). CONCLUSIONS: Three-dimensional ultrasound allows measurement of fetal liver volume, and this demonstrated an approximately 14-fold increase during the second half of pregnancy. It is speculated that three-dimensional fetal liver volume measurement may identify the fetus at risk of growth restriction.

Respiratory and metabolic responses to endurance cycle exercise in pregnant and postpartum women.

This study was designed to determine whether endurance cycling responses in pregnancy differ from those postpartum. We studied 16 women longitudinally at approximately 32 wk pregnancy and approximately 10 wk postpartum. We measured heart rate (HR), O2 uptake (VO2), CO2 output (VCO2), minute ventilation VE and plasma concentrations of substrates and of catecholamines at rest, during maximal testing, and during approximately 35-40 min of cycling at approximately 70-75% VO2peak. Endurance exercise time and power were 37.6+/-1.0 min and 124+/-8 W in pregnancy, similar to values observed postpartum. HR and respiratory responses near the end of endurance exercise were also unaffected by gestation, with pregnancy values of 173+/-3 bpm, 1.87+/-0.07 L/min VO2, and 1.68+/-0.07 L/min VCO2, except that VE at 70.0+/-3.5 L/min was 14% higher than postpartum; plasma concentrations of free fatty acids (404+/-62 micromol/L), glucose (3.34+/-0.17 mmol/L), and lactic acid (4.51+/-0.50 mmol/L) were lower than postpartum by 9, 24, and 19%, respectively; catecholamine concentrations were not different from those determined postpartum. We conclude that pregnant women are equally capable as are postpartum women to perform approximately 40 min of cycling at 70-75% VO2peak, and that the physiologic responses to endurance exercise are largely independent of gestation.

Circulating bioactive tumor necrosis factor-alpha, tumor necrosis factor-alpha receptors, fibronectin, and tumor necrosis factor-alpha inducible cell adhesion molecule VCAM-1 in uncomplicated pregnancy.

OBJECTIVES: Our goal was to assess in a longitudinal study of uncomplicated pregnancy the course of maternal plasma concentrations of the bioactive cytokine tumor necrosis factor-alpha, the soluble tumor necrosis factor-alpha receptors sTNFRI and sTNFRII, the soluble cell adhesion molecule sVCAM-1, and circulating fibronectin. STUDY DESIGN: Blood was collected from 22 healthy pregnant women at 7 to 17, 18 to 22, 23 to 28, and 30 to 36 weeks' gestation and post partum. Plasma samples were measured by bioassay for bioactive tumor necrosis factor-alpha, by immunoassay for sTNFRI, sTNFRII, and VCAM-1, and by radial immunodiffusion for circulating fibronectin, and data were statistically analyzed. RESULTS: Plasma concentrations of all variables were significantly linked with gestational age. Levels of bioactive tumor necrosis factor-alpha and sTNFRII showed a parallel rise in the second trimester and a decrease thereafter. Values for sTNFRI and sTNFRII and for these receptors and VCAM-1 were correlated, a weak correlation between bioactive tumor necrosis factor-alpha and sTNFRII was observed, and no correlation between circulating fibronectin and other variables was apparent. CONCLUSIONS: All variables studied exhibited a characteristic pattern depending on gestational age, which supports the concept of a physiologic role of tumor necrosis factor-alpha in pregnancy.

Placental transfer and maternal and fetal hemodynamic effects of ketanserin in the pregnant ewe.

OBJECTIVE: To determine placental transfer of ketanserin and to assess the effect of serotonin-2 receptor blockade by ketanserin on serotonin- and phenylephrine-induced vasoconstriction. STUDY DESIGN: Five chronically instrumented pregnant ewes at 120 days gestation were injected with 20 mg ketanserin i.v., and fetal and maternal arterial samples were obtained at predetermined intervals to assess placental transfer. Maternal and fetal responses of blood flows and pressures were determined after injected of serotonin (20 micrograms/kg) or phenylephrine (10 micrograms/kg) before and after ketanserin (0.75 mg/kg). RESULTS: In the ewe, ketanserin is transferred across the placenta and reaches measurable levels in the fetal lamb. Ketanserin blocks the maternal and fetal serotonin-induced rise in arterial pressure, but not the serotonin-induced reduction in uterine blood flow. CONCLUSION: In the pregnant ewe, the serotonin-induced rise in maternal and fetal blood pressure is effectively antagonized by ketanserin, whereas the serotonin-induced reduction in uterine blood flow is not.

Peak ventilatory responses during cycling and swimming in pregnant and nonpregnant women.

This study was designed to determine whether pregnancy affects peak O2 uptake (VO2peak) during swimming compared with cycling. We studied 11 women at 30-34 wk gestation and 8-12 wk postpartum. We measured heart rate (HR), O2 uptake (VO2), CO2 output (VCO2), minute ventilation (VE), and lactic acid concentration. Peak HR was not significantly affected by the type of exercise or by pregnancy. VO2peak was 9% lower during swimming than during cycling but was not affected by pregnancy, with values for pregnancy cycling, pregnancy swimming, postpartum cycling, and postpartum swimming of 2.36 +/- 0.12, 2.11 +/- 0.11, 2.29 +/- 0.10, and 2.12 +/- 0.07 l/min, respectively. Peak VCO2 (VCO2peak) and peak VE were significantly lower during swimming than during cycling by 18-25%, but only VCO2peak during swimming was affected by pregnancy (-10%). Lactic acid concentrations were 12-17% lower after swimming than after cycling and 17-31% lower during pregnancy than postpartum. We conclude that perceived maximal exertion is reached at a lower percent maximal VO2 in swimming than in cycling and that the reduced energy expenditure is reflected by lower VO2peak, VCO2peak, and peak VE. Pregnancy, however, does not affect VO2peak in cycling or swimming.

Tumor necrosis factor-alpha in response to endotoxin administration in the pregnant guinea pig.

OBJECTIVE: Our purpose was to test the hypothesis that an intramuscular endotoxin challenge induces production of tumor necrosis factor-alpha in the pregnant guinea pig and to investigate some of the metabolic effects. STUDY DESIGN: Twelve randomly selected guinea pigs at 33 days' gestation with a sampling catheter in the carotid artery received an intramuscular injection of a solution of endotoxin isolated from Bacteroides fragilis (n = 6) or of solvent alone (n = 6). Plasma values of tumor necrosis factor-alpha, hematocrit, and 6-keto-prostaglandin F1 alpha were determined before and several hours after injection. RESULTS: Tumor necrosis factor-alpha was detected in five of six guinea pigs, but it could not be demonstrated in five of six placebo animals. The hematocrit was significantly decreased, and prostaglandin F1 alpha significantly increased 24 to 48 hours after endotoxin injection. CONCLUSION: In pregnant guinea pigs an intramuscular endotoxin challenge induces the release of tumor necrosis factor-alpha, followed by a reduced hematocrit and an increased prostacyclin concentration. These effects could be involved in the pathogenesis of endotoxin-induced fetal growth retardation.

Fetal heart rate and uterine contractility during maternal exercise at term.

OBJECTIVE: Our aim was to assess the physiologic response of human fetal heart rate and uterine contractility to moderately strenuous maternal exercise. STUDY DESIGN: We measured fetal heart rate and intrauterine pressure with the use of internal monitoring before, during, and after maternal exercise at a heart rate of 140 beats/min on a cycle ergometer in 30 term women admitted for elective induction of labor. The fetal heart rate tracings were assessed by three observers and were classified according to Fischer et al. and Nijhuis et al., and the frequency and intensity of uterine contractions were determined. RESULTS: Fetal outcome was good in all cases. There were no significant differences in Fischer scores between rest, exercise, and recovery periods. The fetuses displayed a heart rate pattern A and B, indicative of behavioral states 1F or 2F, 85% of the time, with state changes apparently independent of exercise. Uterine activity increased significantly during the exercise period, with a 5.5-fold increase in contraction frequency and a fourfold increase in time-pressure integral compared with rest, with rapid recovery after the exercise. CONCLUSION: Exercise in healthy pregnant women at term does not cause a change in fetal heart rate pattern suggestive of fetal distress or a change in fetal behavioral pattern, but it does significantly increase uterine activity.

Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe pre-eclampsia remote from term.

OBJECTIVE: To assess maternal and perinatal outcomes of expectant management with plasma volume expansion and pharmacologic vasodilatation in patients with severe pre-eclampsia remote from term. STUDY DESIGN: All women with severe pre-eclampsia between 20 and 32 weeks' gestation, not in labor and with a live, single fetus admitted to the University Hospital Rotterdam from 1985 to 1993 were managed with the intention to prolong gestation. Treatment consisted of correction of the maternal circulation with vasodilatation by means of dihydralazine and plasma volume expansion under central hemodynamic monitoring. Primary end-points of the study were prolongation of gestation, maternal antepartum and postpartum complications, and fetal and neonatal outcome. RESULTS: Two-hundred fifty-four patients were included. The median prolongation of pregnancy was 14 (range 0-62) days. Hemodynamic treatment was associated with marked objective and subjective improvement in maternal condition. Complications of central hemodynamic monitoring were not observed. Perinatal mortality was 20.5%. CONCLUSION: Expectant management with plasma volume expansion and pharmacologic vasodilatation under central hemodynamic monitoring of the maternal circulation may delay delivery and enhance fetal maturity and does not appear to be associated with an increased risk of maternal morbidity and mortality.

A comparison between the haemodynamic effects of oral nifedipine and intravenous dihydralazine in patients with severe pre-eclampsia.

OBJECTIVE: To compare the effects of a single oral dose of nifedipine with those of intravenous dihydralazine on central haemodynamics in pregnant women with severe pre-eclampsia. DESIGN: A prospective comparative study. SETTING: The High Risk Obstetric Unit, University Hospital Rotterdam Dijkzigt, Rotterdam. SUBJECTS: Twenty patients with severe pre-eclampsia between 27 and 35 weeks gestation with normal cardiac filling pressures and without fetal distress. INTERVENTIONS: A pulmonary artery thermodilution catheter and a radial artery line were placed. Ten patients chewed a 10-mg capsule of nifedipine and 10 patients received dihydralazine by intravenous infusion at a rate of 1-3 mg/h. Arterial pressures, heart rate, cardiac output and pulmonary capillary wedge pressure were determined before and after drug administration. Fetal condition was continuously monitored by cardiotocography. RESULTS: The reduction in arterial blood pressure obtained with both drugs was similar, and was associated with a similar rise in heart rate and cardiac output and a similar reduction in systemic vascular resistance. Pulmonary capillary wedge pressures decreased significantly less with nifedipine than with dihydralazine. Signs of fetal distress occurred in none of the nifedipine-treated patients, but in five of the patients treated with dihydralazine. CONCLUSION: From the haemodynamic viewpoint nifedipine seems to be a useful agent in the treatment of hypertensive emergencies in pregnancy.

Maternal and perinatal complications in triplet compared with twin pregnancy.

OBJECTIVE: To compare maternal and perinatal complications in triplet and twin pregnancies. STUDY DESIGN: Case-controlled study in the setting of a University Hospital. Each pregnancy of a consecutive series of 40 triplet pregnancies of 20 weeks or more was matched for parity and maternal age with two sets of twins delivered in the same year. Primary end points of the analysis were maternal complications and perinatal outcome. RESULTS: Of the triplets 82% and of the twins 36% were a result of assisted reproduction. Pre-term labor occurred significantly more often in triplet than in twin gestation. Triplets had a significantly lower median birth-weight (1478 vs. 2030 g) and gestational age at delivery (32 vs. 35.5 weeks). The mean neonatal hospital stay was significantly longer in triplets, mainly related to the lower birth-weight, but there was no significant difference between triplets and twins in the incidence of major neonatal complications. CONCLUSION: This data of the anticipated perinatal outcome in triplet and twin pregnancies may be used to counsel women with a triplet pregnancy considering selective reduction to twins. All methods of assisted reproduction should aim at prevention of multifetal gestation.