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Fetal repair of myelomeningocele (MMC) and myeloschisis leads to improved neurologic outcomes compared to postnatal repair, but the effects of modifications in closure techniques have not been extensively studied. Previous work has suggested that a watertight repair is requisite for improvement in hindbrain herniation (HBH) and to decrease postnatal hydrocephalus (HCP). Our institution adopted the myofascial closure technique for open fetal MMC repair in July 2019, which we hypothesized would result in decreased need for patch closure, improved HBH, and decreased rate of surgically-treated HCP.A single-center retrospective study of patients who underwent fetal MMC or myeloschisis repair between March 2013 and February 2022 was performed. Outcomes were evaluated (n = 70 prior to July 2019, n = 34 after July 2019). Statistical significance was determined by Fisher's exact and Chi square tests (p0.05 significant).Patients who underwent myofascial closure were less likely to require a patch for skin closure (14.7% vs 58.6%, p0.0001). Myofascial closure was also associated with an increased rate of HBH improvement on two-week postoperative fetal MRI (93.9% vs 65.7%, p = 0.002). Surgically-treated HCP at one year was lower in the myofascial closure group (n = 21), however this did not reach statistical significance (23.8% vs 41.9%, p = 0.19).We conclude that the myofascial closure technique for repair of fetal MMC and myeloschisis is associated with significantly decreased need for patch closure and improvement in hindbrain herniation compared to our previous skin closure technique. These results support a surgical approach that employs a multilayer watertight closure.

Multifetal gestation pregnancies present a clinical challenge due to unique complications including growth issues, prematurity, maternal risk, and pathologic processes, such as selective intrauterine growth restriction (sIUGR), twin-to-twin transfusion syndrome (TTTS), and twin anemia-polycythemia sequence. If sIUGR is found, then management may involve some combination of increased surveillance, fetal procedures, and/or delivery. The combination of sIUGR with TTTS or other comorbidities increases the risk of pregnancy complications. Multifetal pregnancy reduction is an option when a problem is confined to a single fetus or when weighing the risks and benefits of a multifetal gestation in comparison to a singleton pregnancy.

Gastroschisis is a congenital abdominal wall defect which results in herniation of abdominal contents. The objective of this study was to determine the maternal risk factors for gastroschisis in Colorado.A case-control study was performed using the Birth Registry database from 2007 to 2016. The outcome was gastroschisis, and the main variable was maternal age which was divided into21, 21-30, and30 years of age. Descriptive analysis, bivariate analysis, and logistic regression was performed.There were 236 cases of gastroschisis compared to 944 controls. Maternal age did vary significantly between groups (23.4 ± 5 years (cases) vs. 28.7 ± 5.9 years (controls); p 0.0001). Unadjusted analysis demonstrated that those with young maternal age (21 years of age) had a 14.14 (95% CI 8.44-23.67) higher odds of gastroschisis compared to those30 years of age. Independent risk factors for gastroschisis were exposure to prenatal and first trimester cigarettes, prenatal and first trimester alcohol, and chlamydia infection. The odds (4.41, 95% CI 1.36-14.26) of gastroschisis were highest in those with first trimester cigarette exposure and young maternal age (p = 0.03).Young maternal age, cigarette exposure, alcohol exposure, and chlamydia infection increase the odds of gastroschisis. The interaction between young maternal age and first trimester cigarette exposure significantly increases the odds of gastroschisis.Prognosis Study.Level III.

Background For pregnancies complicated by fetal myelomeningocele who meet the established criteria, prenatal closure is a viable management option. Prenatal closure is an open procedure, with some techniques requiring greater dissection of maternal tissue than cesarean delivery; pain control is an important postoperative goal. Given the rising rates of opioid dependence and concerns regarding the fetal and neonatal effects of opioid use, our practice has turned to nonopioid pain management techniques. Objective This study aimed to compare postoperative opioid use and pain scores in women undergoing open fetal myelomeningocele repair with and without continuous local bupivacaine wound infusion. Study Design This was a retrospective, single-center chart review of all consecutive patients who underwent open myelomeningocele repair from March 2013 to December 2019. Women were enrolled at the time of referral and locally followed for 2 weeks postoperatively. The control group received patient-controlled epidural analgesia for 48 hours with acetaminophen and oral and intravenous opioids as needed. The treatment group received patient-controlled epidural analgesia for 24 hours with acetaminophen, oral and intravenous opioids, and continuous local bupivacaine infusion. Pain scores, medication use, and postoperative milestones and complications through discharge were abstracted from the chart and compared. Results Of 72 subjects, 51 were in the control group and 21 in the treatment group. Total opioid use, including intravenous doses (165 vs 52.5 mg; P=.001) and daily average oral opioid use (30 vs 10.5 mg; P=.002) were lower in the treatment group. In addition, 24% of women in the treatment group used no opioid postoperatively, compared with 4% in the control group. There was no difference in postoperative day 1 to 4 pain scores, antiemetic use, or bowel function; the treatment group was discharged significantly earlier. Conclusion Postoperative opioid use was reduced in women who received continuous local wound infusion of bupivacaine for incisional pain control after prenatal myelomeningocele repair. Pain control is paramount following open myelomeningocele repair; local bupivacaine wound infusion is an important adjunct to reduce opioid use postoperatively.

Use of oral agents to treat gestational diabetes mellitus remains controversial. Recent recommendations from the Society for Maternal-Fetal Medicine assert that metformin may be a safe first-line alternative to insulin for gestational diabetes mellitus treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of metformin use during pregnancy. Fetal concentrations of metformin are equal to maternal, and metformin can inhibit growth, suppress mitochondrial respiration, have epigenetic modifications on gene expression, mimic fetal nutrient restriction, and alter postnatal gluconeogenic responses. Because both the placenta and fetus express metformin transporters and exhibit high mitochondrial activity, these properties raise important questions about developmental programming of metabolic disease in offspring. Animal studies have demonstrated that prenatal metformin exposure results in adverse long-term outcomes on body weight and metabolism. Two recent clinical randomized controlled trials in women with gestational diabetes mellitus or polycystic ovary syndrome provide evidence that metformin exposure in utero may produce a metabolic phenotype that increases childhood weight or obesity. These developmental programming effects challenge the conclusion that metformin is equivalent to insulin. Although the Society for Maternal-Fetal Medicine statement endorsed metformin over glyburide if oral agents are used, there are few studies directly comparing the 2 agents and it is not clear that metformin alone is superior to glyburide. Moreover, it should be noted that prior clinical studies have dosed glyburide in a manner inconsistent with its pharmacokinetic properties, resulting in poor glycemic control and high rates of maternal hypoglycemia. We concur with the American Diabetes Association and American Congress of Obstetricians and Gynecologists, which recommend insulin as the preferred agent, but we believe that it is premature to embrace metformin as equivalent to insulin or superior to glyburide. Due to the uncertainty of the long-term metabolic risks of either metformin or glyburide, we call for carefully controlled studies that optimize oral medication dosing according to their pharmacodynamic and pharmacokinetic properties in pregnancy, appropriately target medications based on individual patterns of hyperglycemia, and follow the offspring long-term for metabolic risk.

Accurate gestational dating is one of the most important assessments obstetrical providers make in pregnancy, given that all of the various management strategies are dependent on knowing where the patient is in gestation. In addition to traditional biometry, ancillary biometric and nonbiometric measurements can help narrow the biologic variability between fetuses. Moreover, one can employ these nontraditional measurements both in late gestation to assist in determining appropriate gestational age and fetal lung maturity, and in other specific clinical situations-such as oligohydramnios, in which compression of the fetal head and abdomen can lead to difficulty in obtaining an accurate biparietal diameter and abdominal circumference. This chapter focuses on nontraditional fetal ultrasound measurements, including the transverse cerebellar diameter, fetal foot length, ratios of biometric and nonbiometric measurements, epiphyseal ossification centers, amniotic fluid volume, placental grading, and other miscellaneous markers in the context of evaluating a fetus with possible intrauterine growth restriction.

Shoulder dystocia has no consensus definition or management algorithm. Its incidence ranges from 0.2% to 3% and its occurrence is unpredictable. Risk factors for shoulder dystocia may include macrosomia, maternal diabetes, operative vaginal delivery, history of macrosomic infant or shoulder dystocia, labor abnormalities, post-term pregnancy, maternal obesity, advanced maternal age, fetal anthropometric variations, and male fetal gender. Once identified, multiple maneuvers can be applied in a stepwise fashion in an attempt to alleviate the dystocia. While training clinicians to manage shoulder dystocia is difficult because of its rare occurrence and lack of standardized management, all clinicians must be able to manage shoulder dystocia at any time.

Severe fetal growth restriction (FGR) is often associated with hypoxia. We studied FGR hypoxia in an experimental model which is produced by exposing pregnant ewes to a hyperthermic environment. The study utilized simultaneous measurements of several relevant factors, e.g., uterine and umbilical blood flows and O(2) uptakes. Sixteen ewes were divided equally into control (C) and hyperthermic (HT) groups. Hyperthermia (40 degrees C for 12h/35 degrees C for 12h; approximately 35% relative humidity, RH) was maintained for 80 days commencing at approximately 38 days gestational age (dGA term 147+/-3 days). All ewes were then placed in a control environment ( approximately 21 degrees C, 24h; approximately 30% RH) and studied at approximately 134 dGA. Mean HT placental and fetal weights were 39% and 45% of C, respectively (p0.0001), umbilical O(2) uptake/kg fetus was 76% of C (p0.01) and umbilical venous PO(2) was reduced (20.2 vs. 29.7 Torr, p0.001). Contrary to the hypothesis that FGR hypoxia is due to maternal placental hypoperfusion, uterine flow was not reduced in relation to O(2) uptake. The uterine-umbilical venous PO(2) difference was enlarged (38 vs. 23 Torr, p0.0001). This difference is the expression of a balance between developmental changes in placental structure and oxidative metabolism, which have opposite effects in terms of fetal oxygenation. We postulate that FGR hypoxia results from disproportionate underdevelopment of those changes which allow for a progressive increase in umbilical O(2) uptake.

Objective The objective of the study was to evaluate endothelial nitric oxide synthase concentration in the placenta, uterine, and umbilical vessels near term in an ovine model of intrauterine growth restriction induced by hyperthermia beginning in early gestation. Study design Four pregnant ewes were exposed to hyperthermia conditions for 80 days beginning at 35 days gestation to induce intrauterine growth restriction. Four ewes were kept in ambient conditions as controls. Umbilical artery Doppler systolic to diastolic ratios were calculated. At 128 days gestation, fetal catheters were placed for aortic blood pressure measurements and blood gas determination. At 132 days gestation, fetal mean systemic blood pressure and gases were determined. Sheep placentomes, umbilical artery and vein, and uterine artery were assessed for endothelial nitric oxide synthase concentration and immunolocalization. Results Compared with control pregnancies, the intrauterine growth restriction pregnancies showed: (1) reduced fetal and placental weights ( P ≤ .01); (2) elevated systemic blood pressure (41 ± 1.53 mm Hg versus 44.3 ± 1.71 mm Hg; P ≤ .05) and systolic to diastolic ratios (3.0 ± 0.34 versus 3.8 ± 0.18; P ≤ .01); (3) reduced fetal O 2 saturation (52.2 ± 7.03% versus 33.05 ± 10.98%; P ≤ .008); and (4) decreased endothelial nitric oxide synthase protein concentration in the umbilical artery (2.7-fold; P ≤ .01) and a trend for a decrease in the uterine artery (1.4-fold; P ≤ .1). Conclusion We conclude that placental endothelial nitric oxide synthase protein concentration is increased near term in our ovine model of intrauterine growth restriction, and that this increase may be secondary to hypoxia.

Objective Our objective was to test the hypothesis that systemic blood pressure (BP) is increased above normal in intrauterine growth restricted (IUGR) fetal lambs with elevated umbilical artery (UmA) Doppler indices. Study design Five pregnant ewes were exposed to hyperthermic conditions for 80 days beginning at 40 days' gestation (dGA) to induce IUGR. They were then placed in ambient conditions with 6 additional ewes that served as controls. Doppler indices were calculated from UmA Doppler flow velocity waveforms. At 128 dGA, fetal catheters were placed for measurement of umbilical blood flow (UBF) by an ethyl alcohol steady-state diffusion technique and for aortic BP measurements. At 132 dGA, fetal mean systemic BP and blood flow were determined. At necropsy the placental and fetal weights were recorded. UBF was normalized for fetal weight. Linear regression, F tests and t tests were performed as appropriate. P Results Compared with control pregnancies, the IUGR pregnancies showed: (1) reduced fetal and placental weights, (2) elevated systemic BP, (3) reduced UBF, (4) elevated UmA and aortic Doppler velocimetry indices, (5) increased resistance per 100 g placenta, and (6) decreased UmA oxygenation and increased lactic academia. The UmA Doppler index of resistance (systolic/diastolic ratio) correlated strongly with calculated resistance (R2 = 0.7). Doppler indices also correlated with systemic BP (R2 = 0.5). Conclusion Ovine IUGR fetuses with high UmA Doppler indices have elevated systemic BPs. UmA Doppler indices of resistance correlate well with (1) fetal systemic BPs and (2) resistance as calculated by pressure/flow. This whole animal study shows that IUGR fetuses are hypertensive and that increased UmA Doppler resistance indices are consistent with a fetal-placental hypertensive state.

This article reviews the complications, management and prognosis of cardiac disease in pregnancy.

OBJECTIVE: To test the hypothesis that reduced birth weight in normal fetuses born at moderately high altitude (Denver), compared with the birth weight in normal fetuses born at sea level (Milan), is caused by a reduction in both lean mass and subcutaneous fat mass. STUDY DESIGN: Ninety-four normal singleton pregnancies (46 in Denver, 48 in Milan) had serial ultrasonographic axial images obtained to assess subcutaneous tissues of fetuses as a measure of body fat. The abdominal wall thickness and mid upper arm and mid thigh were examined. The equation was: Subcutaneous tissue equals total cross-sectional area minus bone and muscle area. Lean mass included the area of muscle and bone, head circumference, and femur length. RESULTS: Gestational age at delivery was similar between groups. Birth weight was less at Denver’s altitude (2991 ± 79 g versus 3247 ± 96 g; P = .04). Abdominal wall thickness, mid upper arm, and mid thigh subcutaneous tissues measurements were significantly reduced at Denver’s altitude and increased further in significance with advancing gestational age. Lean mass measurements were similar between groups. CONCLUSIONS: The reduced birth weight of the newborns in Denver was the result of a reduction in fetal subcutaneous fat tissue and not lean mass. Ultrasonography can be used to follow subcutaneous measurements longitudinally and to detect differences, and potentially disease processes, in study populations. (Am J Obstet Gynecol 2001;185:839-44.)

Objective: This study was undertaken to assess the accuracy of triplex ultrasonographic measurement of venous umbilical blood flow in comparison with the steady-state diffusion technique and to determine the impact of cotyledon weight and number on umbilical blood flow. Study Design: Six late-gestation ewes with long-term catheter placement were studied for venous umbilical blood flow with the ethanol steady-state diffusion technique and with triplex-mode ultrasonography (color Doppler, pulsed-wave Doppler, and real-time ultrasonography). At necropsy the number and weight of the cotyledons serving each umbilical vein were recorded. Results: Umbilical blood flow determined by triplex-mode ultrasonography (207.5 ± 8.6 mL · kg –1 fetus · min –1 ) was virtually identical to that determined with the steady-state diffusion technique (208.1 ± 7.3 mL · kg –1 fetus · min –1 ; P = .9). When values were normalized for the weight or number of cotyledons serving each vein, there was no difference in umbilical blood flow between small and large umbilical veins in all the sheep. Conclusions: Our study validates the accuracy of the triplex ultrasonographic method and provides justification for its use in future human investigations. In absolute terms umbilical blood flow frequently differs between the 2 veins. When expressed per number or mass of cotyledons, however, the umbilical blood flows are similar. (Am J Obstet Gynecol 1999;181:1149-53.)

With an ovine model in which growth restriction was induced by exposure to heat stress, our aims were as follows: (1) to describe the normal gestational age-related changes in Doppler velocimetry in the ovine fetal aorta and umbilical artery and (2) to compare Doppler velocimetry between heat-stressed and non-heat-stressed fetuses.Five ewes were exposed to heat stress for 55 days beginning at 35 days' gestation. Five ewes were not exposed and served as controls. Aortic and umbilical artery pulsed Doppler velocimetry was obtained, including the systolic/diastolic ratio, pulsatility index, and resistance index. Data were obtained between 50 and 120 days' gestation. Linear regression analysis was used to analyze gestational age-related changes in velocimetry. Comparison of mean index values between heat-stressed and non-heat-stressed fetuses were made with analysis of variance.Heat-stressed fetuses demonstrated significantly higher systolic/diastolic ratios and pulsatility index values for both umbilical artery (p0.025; p0.033) and aorta (p0.017; p0.022) compared with controls. The umbilical artery and aortic resistance index values were not different between groups (p0.079; p0.28). The slopes for each of the Doppler index values were negative in both normal and heat-stressed fetuses. Umbilical artery and aortic end-diastolic flows remained absent through the first 70 days of gestation in both groups.Doppler velocimetry index values decrease with increasing gestational age, reflecting decreased placental bed vascular resistance. The higher Doppler index values seen in the heat-stressed group are consistent with increased placental vascular resistance. The normal absence of diastolic flow until 70 days' gestation is similar to the pattern described in humans.

Whether fetal breathing movements or gasping result in the movement of amniotic fluid substances into the distal airways remains controversial. We evaluated the effect of paralysis of the preterm rabbit fetus on the pulmonary distribution of iron dextran.Laparotomy was performed on 10 New Zealand White rabbits of 25 days' gestation (term 31 days) under general anesthesia. Fetuses in one uterine horn were given an intramuscular injection of pancuronium (1.5 mg/kg) and fetuses in the other horn were given an equal volume of normal saline solution as controls. A 1 ml volume of iron dextran (100 mg/ml) was injected into the amniotic sac of all fetuses. The laparotomy was closed, and 20 to 24 hours later the fetuses were removed by hysterotomy and assessed for paralysis. Necropsy was performed. Lungs were stained with prussian blue and evaluated histologically for the presence of iron.A total of 92 pups were delivered (49 given pancuronium, 43 given normal saline solution), of which 64 were born alive. There were no differences between groups for live births (31 pancuronium, 33 normal saline solution), pup body weight, or lung weight. Pups given normal saline solution demonstrated more breathing motions, spontaneous movement, and brown (color of iron dextran) stomach contents than did the pups given pancuronium (p0.001). At necropsy a greater number of control pups (31/33) had brown lungs grossly compared with pups given pancuronium (2/31, p0.001). Lung histologic examination showed that more control pups (29/29) had iron in the trachea and main bronchi compared with pancuronium pups (0/27, p0.001), and more control pups (29/29) had iron in the distal lung airways compared with pancuronium pups (0/27, p0.001). With use of the Optimas Image Analysis System, iron in the lungs of control pups was found to be equally distributed between right versus left lungs, upper half versus lower half lungs, and anterior versus posterior lung sections. More iron was identified in the central airways than in the periphery (p0.001).We conclude that paralysis prevents the uptake of iron dextran into the main and distal airways of the rabbit fetus. Although lung fluid production results in a net efflux of fluid, we speculate that fetal breathing movements can result in the movement of fluid into distal airways and potentially provide fetal therapy.

To test the hypothesis that intraabdominal pressures (IAP) associated with abdominal insufflation for laparoscopic procedures can alter pulmonary and hemodynamic values in the pregnant baboon and hemodynamic values in the fetus.A descriptive physiologic study.Animal research facility at Scott and White Memorial Hospital, Temple, TX.Four pregnant baboons at 120 +/- 7 days' gestation.The baboons underwent general anesthesia, Swan-Ganz and arterial catheter placement, and abdominal insufflation at 10 and 20 mm Hg IAP for 20-minute intervals at each pressure. The following end points were measured: maternal heart rate (MHR), mean arterial pressure (MAP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), pulmonary artery pressures (PAP), central venous pressure (CVP), systemic vascular resistance (SVR), ventilator rate (VR), oxygen saturation, and end-tidal carbon dioxide (CO2). Fetal heart rate and fetal growth values were measured, and umbilical artery Doppler flow studies were performed.The PCWP (p0.026), CVP (p0.0012), and PAP (p0.046) were significantly increased at 20 mm Hg IAP; CO decreased as IP increased. The MAP, MHR, and SVR did not change significantly with increased IAP. The only significant change in pulmonary values was the increase in peak airway pressure (p0.001). The VR was increased from an average of 18 to 41 breaths/minute in an attempt to maintain adequate oxygen saturation and to normalize end-tidal CO2 when IAP was increased to 20 mm Hg. Respiratory acidosis (pH7. 35, partial pressure of carbon dioxide50 torr) was demonstrated in three of four animals within 20 minutes at an IAP of 20 mm Hg. Results of Doppler flow studies on the effects of the fetuses were unaltered immediately after this procedure compared with baseline measurements. Normal interval growth was demonstrated 2 weeks after the procedure.The baboon mothers and fetuses had no adverse effects at an IAP of 10 mm Hg, but may have significant cardiovascular and respiratory alterations associated with IAP of 20 mm Hg.