The role of nitric oxide in the cardiopulmonary response to hypoxia in highland and lowland newborn llamas.

KEY POINTS: Perinatal hypoxia causes pulmonary hypertension in neonates, including humans. However, in species adapted to hypoxia, such as the llama, there is protection against pulmonary hypertension. Nitric oxide (NO) is a vasodilatator with an established role in the cardiopulmonary system of many species, but its function in the hypoxic pulmonary vasoconstrictor response in the newborn llama is unknown. Therefore, we studied the role of NO in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas. We show that high- compared to lowland newborn llamas have a reduced pulmonary vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary vasoconstriction in the highland llama is mediated via enhancement of NO pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+ desensitization. Blunting of pulmonary hypertensive responses to hypoxia through enhanced NO pathways may be an adaptive mechanism to withstand life at high altitude in the newborn llama. ABSTRACT: Llamas are born in the Alto Andino with protection against pulmonary hypertension. The physiology underlying protection against pulmonary vasoconstrictor responses to acute hypoxia in highland species is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas. The cardiopulmonary function of newborn llamas born at low (580 m) or high altitude (3600 m) was studied under acute hypoxia, with and without NO blockade. In pulmonary arteries, we measured the reactivity to potassium and sodium nitroprusside (SNP), and in lung we determined the content of cGMP and the expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and 2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary vascular remodelling was evaluated by morphometry and based on α-actin expression. High- compared to lowland newborn llamas showed lower in vivo pulmonary arterial pressor responses to acute hypoxia. This protection involved enhanced NO function, as NO blockade reverted the effect and the pulmonary arterial dilatator response to SNP was significantly enhanced in highland neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were lower in high-altitude llamas. Conversely, MYPT1 was up-regulated whilst PSer695-MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were insufficient to prevent pulmonary arterial remodelling. Combined, the data strongly support that in the highland newborn llama reduced ROCK, increased MYPT1 expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic pulmonary hypertensive responses may be an adaptive mechanism to life at high altitude.

Cardiovascular function in term fetal sheep conceived, gestated and studied in the hypobaric hypoxia of the Andean altiplano.

High-altitude hypoxia causes intrauterine growth restriction and cardiovascular programming. However, adult humans and animals that have evolved at altitude show certain protection against the effects of chronic hypoxia. Whether the highland fetus shows similar protection against high altitude gestation is unclear. We tested the hypothesis that high-altitude fetal sheep have evolved cardiovascular compensatory mechanisms to withstand chronic hypoxia that are different from lowland sheep. We studied seven high-altitude (HA; 3600 m) and eight low-altitude (LA; 520 m) pregnant sheep at ∼90% gestation. Pregnant ewes and fetuses were instrumented for cardiovascular investigation. A three-period experimental protocol was performed in vivo: 30 min of basal, 1 h of acute superimposed hypoxia (∼10% O2) and 30 min of recovery. Further, we determined ex vivo fetal cerebral and femoral arterial function. HA pregnancy led to chronic fetal hypoxia, growth restriction and altered cardiovascular function. During acute superimposed hypoxia, LA fetuses redistributed blood flow favouring the brain, heart and adrenals, whereas HA fetuses showed a blunted cardiovascular response. Importantly, HA fetuses have a marked reduction in umbilical blood flow versus LA. Isolated cerebral arteries from HA fetuses showed a higher contractile capacity but a diminished response to catecholamines. In contrast, femoral arteries from HA fetuses showed decreased contractile capacity and increased adrenergic contractility. The blunting of the cardiovascular responses to hypoxia in fetuses raised in the Alto Andino may indicate a change in control strategy triggered by chronic hypoxia, switching towards compensatory mechanisms that are more cost-effective in terms of oxygen uptake.

Role of the RhoA/ROCK pathway in high-altitude associated neonatal pulmonary hypertension in lambs.

Exposure to high-altitude chronic hypoxia during pregnancy may cause pulmonary hypertension in neonates, as a result of vasoconstriction and vascular remodeling. We hypothesized that susceptibility to pulmonary hypertension, due to an augmented expression and activity of the RhoA/Rho-kinase (ROCK) pathway in these neonates, can be reduced by daily administration of fasudil, a ROCK inhibitor. We studied 10 highland newborn lambs with conception, gestation, and birth at 3,600 m in Putre, Chile. Five highland controls (HLC) were compared with 5 highland lambs treated with fasudil (HL-FAS; 3 mg·kg(-1)·day(-1) iv for 10 days). Ten lowland controls were studied in Lluta (50 m; LLC). During the 10 days of fasudil daily administration, the drug decreased pulmonary arterial pressure (PAP) and resistance (PVR), basally and during a superimposed episode of acute hypoxia. HL-FAS small pulmonary arteries showed diminished muscular area and a reduced contractile response to the thromboxane analog U46619 compared with HLC. Hypoxia, but not fasudil, changed the protein expression pattern of the RhoA/ROCKII pathway. Moreover, HL-FAS lungs expressed less pMYPT1(T850) and pMYPT1T(696) than HLC, with a potential increase of the myosin light chain phosphatase activity. Finally, hypoxia induced RhoA, ROCKII, and PKG mRNA expression in PASMCs of HLC, but fasudil reduced them (HL-FAS) similarly to LLC. We conclude that fasudil decreases the function of the RhoA/ROCK pathway, reducing the PAP and PVR in chronically hypoxic highland neonatal lambs. The inhibition of ROCKs by fasudil may offer a possible therapeutic tool for the pulmonary hypertension of the neonates.

Should we really avoid giving oxygen to mothers with concerning fetal heart rate patterns?

We challenge a provocative article entitled "Oxygen for intrauterine resuscitation: of unproved benefit and potentially harmful" by Hamel et al in the August issue of the Journal. The authors contend there is no good evidence that oxygen administration to the mother of a fetus with a concerning fetal heart rate pattern prevents acidosis and that in theory such oxygen administration may actually or potentially do harm to the fetus. It is clear that oxygen is administered quite often to women in labor, especially to those with category II fetal heart rate patterns and, because more than 80% of women in labor have these patterns and the majority of these patterns are unlikely to be associated with significant fetal hypoxia, that such oxygen administration is greatly overused. We describe in this article evidence that oxygen given to the mother actually does improve fetal oxygenation, especially in hypoxemic fetuses, and make arguments that there really is no substantial evidence that, except in theory, maternal oxygen administration causes any harm to the fetus.

Melatonin improves cerebrovascular function and decreases oxidative stress in chronically hypoxic lambs.

Chronic hypoxia during gestation and delivery results in oxidative stress and cerebrovascular dysfunction in the neonate. We assessed whether melatonin, a potent antioxidant and potential vasodilator, improves the cerebral vascular function in chronically hypoxic neonatal lambs gestated and born in the highlands (3600 m). Six lambs received melatonin (1 mg/kg per day oral) and six received vehicle, once a day for 8 days. During treatment, biometry and hemodynamic variables were recorded. After treatment, lambs were submitted to a graded FiO2 protocol to assess cardiovascular responses to oxygenation changes. At 12 days old, middle cerebral arteries (MCA) were collected for vascular reactivity, morphostructural, and immunostaining evaluation. Melatonin increased fractional growth at the beginning and improved carotid blood flow at all arterial PO2 levels by the end of the treatment (P < 0.05). Further, melatonin treatment improved vascular responses to potassium, serotonin, methacholine, and melatonin itself (P < 0.05). In addition, melatonin enhanced the endothelial response via nitric oxide-independent mechanisms in isolated arteries (162 ± 26 versus 266 ± 34 AUC, P < 0.05). Finally, nitrotyrosine staining as an oxidative stress marker decreased in the MCA media layer of melatonin-treated animals (0.01357 ± 0.00089 versus 0.00837 ± 0.00164 pixels/µm2 , P < 0.05). All the melatonin-induced changes were associated with no systemic cardiovascular alterations in vivo. In conclusion, oral treatment with melatonin modulates cerebral vascular function, resulting in a better cerebral perfusion and reduced oxidative stress in the neonatal period in chronically hypoxic lambs. Melatonin is a potential therapeutic agent for treating cerebrovascular dysfunction associated with oxidative stress and developmental hypoxia in neonates.

Store-operated channels in the pulmonary circulation of high- and low-altitude neonatal lambs.

We determined whether store-operated channels (SOC) are involved in neonatal pulmonary artery function under conditions of acute and chronic hypoxia, using newborn sheep gestated and born either at high altitude (HA, 3,600 m) or low altitude (LA, 520 m). Cardiopulmonary variables were recorded in vivo, with and without SOC blockade by 2-aminoethyldiphenylborinate (2-APB), during basal or acute hypoxic conditions. 2-APB did not have effects on basal mean pulmonary arterial pressure (mPAP), cardiac output, systemic arterial blood pressure, or systemic vascular resistance in both groups of neonates. During acute hypoxia 2-APB reduced mPAP and pulmonary vascular resistance in LA and HA, but this reduction was greater in HA. In addition, isolated pulmonary arteries mounted in a wire myograph were assessed for vascular reactivity. HA arteries showed a greater relaxation and sensitivity to SOC blockers than LA arteries. The pulmonary expression of two SOC-forming subunits, TRPC4 and STIM1, was upregulated in HA. Taken together, our results show that SOC contribute to hypoxic pulmonary vasoconstriction in newborn sheep and that SOC are upregulated by chronic hypoxia. Therefore, SOC may contribute to the development of neonatal pulmonary hypertension. We propose SOC channels could be potential targets to treat neonatal pulmonary hypertension.

Intrapartum management of category II fetal heart rate tracings: towards standardization of care.

There is currently no standard national approach to the management of category II fetal heart rate (FHR) patterns, yet such patterns occur in the majority of fetuses in labor. Under such circumstances, it would be difficult to demonstrate the clinical efficacy of FHR monitoring even if this technique had immense intrinsic value, since there has never been a standard hypothesis to test dealing with interpretation and management of these abnormal patterns. We present an algorithm for the management of category II FHR patterns that reflects a synthesis of available evidence and current scientific thought. Use of this algorithm represents one way for the clinician to comply with the standard of care, and may enhance our overall ability to define the benefits of intrapartum FHR monitoring.

Role of the α-adrenergic system in femoral vascular reactivity in neonatal llamas and sheep: a comparative study between highland and lowland species.

Using an integrative approach at the whole animal, isolated vessels, and molecular levels, we tested the hypothesis that the llama, a species that undergoes pregnancy under the influence of the chronic hypoxia of high altitude, delivers offspring with an increased α-adrenergic peripheral vascular reactivity compared with neonates from lowland species. We studied the femoral vascular response to acute hypoxia in vivo, the reactivity of femoral vessels ex vivo, and the expression of femoral α(1)-adrenergic receptor subtypes using RT-PCR in vitro. The increase in femoral resistance during hypoxia was 3.6 times greater in newborn llamas than newborn sheep (P < 0.05). The sensitivity of the contractile response to noradrenaline (pD(2) = 5.18 ± 0.06 vs. 4.84 ± 0.05, P < 0.05) and the maximal response (R(max) = 101.3 ± 1.4 vs. 52.4 ± 1.4% K(+)(max), P < 0.05) and sensitivity (pD(2) = 5.47 ± 0.03 vs. 4.57 ± 0.05, P < 0.05) to phenylephrine were higher in femoral vessels from newborn llamas than newborn sheep. Competitive inhibition with prazosin of noradrenaline-induced contraction followed by Schild analysis showed higher affinity in the llama than the sheep (pA(2) = 10.08 ± 0.093 vs. 8.98 ± 0.263, respectively, P < 0.05), consistent with greater α(1B)-adrenergic receptor transcript expression observed in small femoral arteries from neonatal llama. The llama newborn demonstrates significantly greater α-adrenergic peripheral vascular reactivity compared with neonates from lowland species that could be partially explained by preferential expression of α(1B)-adrenergic receptor subtype.

Long-term exposure to high-altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level.

We determined whether postnatal pulmonary hypertension induced by 70% of pregnancy at high altitude (HA) persists once the offspring return to sea level and investigated pulmonary vascular mechanisms operating under these circumstances. Pregnant ewes were divided into two groups: conception, pregnancy, and delivery at low altitude (580 m, LLL) and conception at low altitude, pregnancy at HA (3,600 m) from 30% of gestation until delivery, and return to lowland (LHL). Pulmonary arterial pressure (PAP) was measured in vivo. Vascular reactivity and morphometry were assessed in small pulmonary arteries (SPA). Protein expression of vascular mediators was determined. LHL lambs had higher basal PAP and a greater increment in PAP after N(G)-nitro-L-arginine methyl ester (20.9 ± 1.1 vs. 13.7 ± 0.5 mmHg; 39.9 ± 5.0 vs. 18.3 ± 1.3 mmHg, respectively). SPA from LHL had a greater maximal contraction to K(+) (1.34 ± 0.05 vs. 1.16 ± 0.05 N/m), higher sensitivity to endothelin-1 and nitroprusside, and persistence of dilatation following blockade of soluble guanylate cyclase. The heart ratio of the right ventricle-to-left ventricle plus septum was higher in the LHL relative to LLL. The muscle area of SPA (29.3 ± 2.9 vs. 21.1 ± 1.7%) and the protein expression of endothelial nitric oxide synthase (1.7 ± 0.1 vs. 1.1 ± 0.2), phosphodiesterase (1.4 ± 0.1 vs. 0.7 ± 0.1), and Ca(2+)-activated K(+) channel (0.76 ± 0.16 vs. 0.30 ± 0.01) were greater in LHL compared with LLL lambs. In contrast, LHL had decreased heme oxygenase-1 expression (0.82 ± 0.26 vs. 2.22 ± 0.44) and carbon monoxide production (all P < 0.05). Postnatal pulmonary hypertension induced by 70% of pregnancy at HA promotes cardiopulmonary remodeling that persists at sea level.

Comparison of 5 experts and computer analysis in rule-based fetal heart rate interpretation.

OBJECTIVE: The purpose of this study was to measure agreement among 5 expert clinicians and a computerized method with the use of a strict fetal heart rate classification method. STUDY DESIGN: Five providers independently scored 769 8-minute segments from the last 3 hours of 30 tracings with the use of a 5-tier color-coded framework that contains pattern descriptions and proposals for management. Computer analysis was performed with PeriCALM Patterns (PeriGen, Princeton, NJ) to detect and classify patterns. RESULTS: The clinicians agreed exactly with the majority opinion in 57% (95% confidence interval [CI], 49-64%) of the segments and were within 1 color code in 89% (95% CI, 81-96%). The average proportion of agreement was 0.83 (95% CI, 0.73-0.94). Weighted Kappa scores averaged 0.58 (range, 0.48-0.68). The computer-based results were not statistically different: 0.87 and 0.52, respectively. CONCLUSION: These 5 clinicians achieved moderate-to-substantial levels of agreement overall using a strictly defined method to classify fetal heart rate tracings. The result of the computerized method was similar to the conclusions of these clinicians.

Spontaneous in utero recovery of a fetus in a brain death-like state.

A healthy pregnant woman at 28 weeks of gestation was admitted with complete loss of fetal movement. Fetal heart rate (FHR) monitoring showed a fixed flat FHR pattern with no variability. Ultrasound examination revealed no fetal breathing movement. The fetus showed heart failure with extremely diminished left heart contractility. No abnormalities were found in the fetus. We assessed that the fetus was in a brain death-like status. After discussion, we decided not to deliver the baby but to monitor it carefully using FHR monitoring and continuous fetal ultrasound examinations, assuming the baby was dying or at least had little possibility of survival. However, 8 h after admission, FHR monitoring showed some variability and after another 12 h the fetus recovered completely. The baby was born at 35 week of gestation by cesarean section. The baby sustained some white matter brain damage, but with no significant clinical delay of motor development. This is a rare case of in utero recovery from a fetal brain death-like status.

The 2008 National Institute of Child Health and Human Development report on fetal heart rate monitoring.

Standardization of fetal heart rate (FHR) interpretation and management guidelines has been elusive, and no system is currently widely accepted in the United States. The recently summarized 2008 Eunice Kennedy Shriver National Institute of Child Health and Human Development workshop proposed a three-tier system of interpretation of FHR patterns, but left management recommendations to the professional associations. The middle tier, called indeterminate Category II, which contains the variant FHR patterns seen most frequently, is vast and heterogeneous. We propose that this category can be subcategorized at least tentatively, based on evidence available from previously published studies. Such subcategorization will allow the organizations proposing management recommendations to more readily set up guidelines for graded interventions and clinical responses to the spectrum of FHR patterns, with the aim of minimizing fetal acidemia without excessive obstetric intervention. Such management algorithms will need to be tested by appropriately designed clinical studies.

Carbon monoxide: a novel pulmonary artery vasodilator in neonatal llamas of the Andean altiplano.

AIMS: To study the nitric oxide (NO) and carbon monoxide roles in the regulation of the pulmonary circulation in lowland and highland newborn sheep and llamas. METHODS AND RESULTS: We used neonatal sheep (Ovis aries) and llamas (Lama glama) whose gestation and delivery took place at low (580 m) or high (3600 m) altitude. In vivo, we measured the cardiopulmonary function basally and with a NO synthase (NOS) blockade and calculated the production of carbon monoxide by the lung. In vitro, we determined NOS and soluble guanylate cyclase (sGC) expression, NOS activity, and haemoxygenase (HO) expression in the lung. Pulmonary arterial pressure was elevated at high altitude in sheep but not in llamas. Sheep at high altitude relative to sea level had significantly greater total lung NOS activity and eNOS protein, but reduced sGC and HO expression and carbon monoxide production. In contrast, llamas showed no difference in NO function between altitudes, but a pronounced increase in pulmonary carbon monoxide production and HO expression at high altitude. CONCLUSIONS: In the llama, enhanced pulmonary carbon monoxide, rather than NO, protects against pulmonary hypertension in the newborn period at high altitude. This shift in pulmonary dilator strategy from NO to carbon monoxide has not been previously described, and it may give insight into new treatments for excessive pulmonary vasoconstriction.

A framework for standardized management of intrapartum fetal heart rate patterns.

OBJECTIVE: The purpose of this study was to classify fetal heart rate (FHR) monitor patterns according to risk of fetal acidemia and risk of evolution to a more serious pattern and to use this information to construct a standardized process for FHR pattern management, with the ultimate aim of minimizing newborn infant acidemia without excessive obstetric intervention. STUDY DESIGN: We have identified 134 FHR patterns that have been classified by baseline rate, baseline variability, and type of deceleration. Based on the best available evidence, we have assigned a risk of newborn infant acidemia or low 5-minute Apgar score to these patterns. We have also evaluated each pattern for the risk that the pattern would evolve further into a pattern with a higher risk of acidemia. RESULTS: Each FHR pattern has been color-coded, from no threat of fetal acidemia (green, no intervention required) to severe threat of acidemia (red, rapid delivery recommended). Three intermediate categories (blue, yellow, and orange) require escalated informing of appropriate individuals for intervention and resuscitation (obstetrician, anesthesiologist, and neonatal resuscitator) and preparation for urgent delivery (eg, staff and surgical suite availability and conservative techniques to ameliorate the FHR patterns). CONCLUSION: This framework is applicable potentially to the institutions where it was developed and will need to be modified for other situations, depending on the logistics, facilities, and personnel available. This may provide a framework for developing algorithms for the standardized management of FHR patterns during labor, which can be tested for validity.

The intrapartum deceleration in center stage: a physiologic approach to the interpretation of fetal heart rate changes in labor.

One of the most distinctive features of fetal heart rate recordings in labor is the deceleration. In clinical practice, there has been much confusion about the types of decelerations and their significance. In the present review, we examined uteroplacental perfusion in labor, describe the pathophysiologic condition of decelerations, and explain some of the reasons behind the confusion about the terminology. We summarize recent studies that systematically have dissected the features of variable decelerations that may help to identify developing fetal compromise, such as the slope of the deceleration, overshoot, and variability changes. Although no pattern of repeated deep decelerations is necessarily benign, fetuses with normal placental reserve can compensate fully, even for frequent deep but brief decelerations, for surprisingly prolonged intervals before the development of profound acidosis and hypotension. This tolerance reflects the remarkable ability of the fetus to adapt to repeated hypoxia. We propose that, rather than focus on descriptive labels, clinicians should be trained to understand the physiologic mechanisms of fetal heart rate decelerations and the patterns of fetal heart rate change that indicate progressive loss of fetal compensation.

Evolving in thin air--lessons from the llama fetus in the altiplano.

Compared with lowland species, fetal life for mammalian species whose mothers live in high altitude is demanding. For instance, fetal llamas have to cope with the low fetal arterial PO2 of all species, but also the likely superimposition of hypoxia as a result of the decreased oxygen environment in which the mother lives in the Andean altiplano. When subjected to acute hypoxia the llama fetus responds with an intense peripheral vasoconstriction mediated by alpha-adrenergic mechanisms plus high plasma concentrations of catecholamines and neuropeptide Y (NPY). Endothelial factors such as NO and endothelin-1 also play a role in the regulation of local blood flows. Unlike fetuses of lowland species such as the sheep, the llama fetus shows a profound cerebral hypometabolic response to hypoxia, decreasing cerebral oxygen consumption, Na-K-ATPase activity and temperature, and resulting in an absence of seizures and apoptosis in neural cells. These strategies may have evolved to prevent hypoxic injury to the brain or other organs in the face of the persistent hypobaric hypoxia of life in the Andean altiplano.

Transabdominal cerclage: can we predict who fails?

OBJECTIVE: To examine the outcome of pregnancies in women with transabdominal cerclage (TAC) and to determine whether aspects of the obstetric history predict failure. METHODS: This was a cohort study of pregnant women referred for a transabdominal cerclage between 1978 and 2004. Records were reviewed for obstetric history and maternal demographics. Predictor variables were prior pregnancy loss, prior vaginal cerclage, associated factors for TAC, and maternal age. The outcome variable was delivery of an infant beyond 24 weeks who survived the neonatal period. Outcomes were compared using Student's t-test, standard z-test, and Chi-square test. RESULTS: Eighty-eight women delivered 96 pregnancies after TAC placement. The fetal salvage rate prior to TAC was 18%, 93% after the procedure (p<0.001). Delivery beyond 37 weeks occurred in 70% of pregnancies. Maternal age, prior cerclage history, associated factors for TAC, or previous delivery of a viable infant did not predict the eight failures out of the 96 pregnancies. CONCLUSION: Women with TAC had a higher rate of successful pregnancies than prior to TAC. Neither maternal age nor prior pregnancy loss predicted failure. However with such a high success rate, we would have needed 948 women to do so. TAC is an option for women with a poor obstetric history including failed vaginal cerclage.

Fetal cerebellar hemorrhage in parvovirus-associated non-immune hydrops fetalis.

We report two cases of fetal cerebellar hemorrhage in the setting of parvovirus-associated hydrops fetalis and fetal blood transfusion. In both cases, the cerebellar hemorrhage was diagnosed by fetal magnetic resonance imaging after intrauterine blood transfusion. To our knowledge, this is the first report of fetal cerebellar hemorrhage in the setting of parvovirus-associated hydrops fetalis, and may be the result of cerebrovascular changes both during and after the transfusion.

Impediments to a unified international approach to the interpretation and management of intrapartum cardiotocographs.

There is much inconsistency in management recommendations for cardiotocograms by international organizations. Impediments to achieving consensus include disagreement on the spectrum of risk of fetal acidemia, different fetal heart rate pattern display due to differing chart paper speed, and the necessity for ancillary testing in confirming fetal acidemia.

Forceps compared with vacuum: rates of neonatal and maternal morbidity.

OBJECTIVE: To compare perinatal outcomes between forceps- and vacuum-assisted deliveries. Our hypothesis was that the force vectors achieved in forceps delivery will lead to fewer shoulder dystocias, but greater perineal lacerations. METHODS: This was a retrospective cohort study of 4,120 term, cephalic, singleton, nonrotational operative vaginal deliveries at a single institution. Outcomes examined included rates of neonatal trauma, shoulder dystocia, and perineal lacerations. Potential confounders, including maternal age, birthweight, ethnicity, parity, station at delivery, episiotomy, attending physician, anesthesia, and length of labor, were controlled for using multivariate logistic regression. RESULTS: Among the 2,075 (50.4%) forceps- and 2,045 (49.6%) vacuum-assisted deliveries, the rate of shoulder dystocia was lower among women undergoing forceps delivery (1.5% compared with 3.5%, P < .001), as was the rate of cephalohematoma (4.5% compared with 14.8%, P < .001), whereas the rate of third- or fourth-degree perineal laceration was higher (36.9% compared with 26.8%, P < .001). These differences in perinatal complications persisted when controlling for the confounders listed above. The adjusted odds ratio for shoulder dystocia was 0.34 (95% confidence interval [CI] 0.20-0.57), for cephalohematoma was 0.25 (95% CI 0.19-0.33), and for third- or fourth-degree lacerations was 1.79 (95% CI 1.52-2.10) when comparing forceps to vacuum. CONCLUSION: Vacuum-assisted vaginal birth is more often associated with shoulder dystocia and cephalohematoma. Forceps delivery is more often associated with third- and fourth-degree perineal lacerations. These differences in complications rates should be considered among other factors when determining the optimal mode of delivery. LEVEL OF EVIDENCE: II-2.