Fetal Growth Restriction

Birthweight below the 10th (small for gestational age or SGA) or above the 90th (large for gestational age or LGA) percentile for gestational age has been associated with adverse maternal, fetal and neonatal outcomes. As birthweight reflects intrauterine development, accurate identification of abnormal fetal growth would allow obstetric providers to prevent adverse outcomes and mitigate complications associated with abnormal development. Symphysis fundal height (SFH) measured in centimeters after 24 weeks of gestation is recommended as the standard of care to screen for fetal growth abnormalities among low-risk pregnancies. This method is low-cost, and easy to perform, but there is a lack of evidence supporting its effectiveness due to its poor sensitivity. Ultrasonography, the technique utilized to identify fetal growth abnormalities, is a costly procedure which involves the use of advanced equipment and providers, to perform and review the ultrasound, as well as a full examination with multiple measurements and images. Despite a few encouraging reports, insufficient evidence supports routine 3rd trimester ultrasound in low- risk pregnancies to improve detection of abnormal fetal growth. Sonographic measurement of the abdominal circumference (AC) in the fetus was shown to be the single most useful indicator of fetal growth. Measurement of AC does not require extensive training, long time to acquire, or expensive ultrasound machines. It can be easily performed in the office by midwives who are specifically trained in obtaining the measurement. Therefore, we intended to evaluate if the use of bedside point of care ultrasound (POC-US) by midwives to evaluate fetal AC during routine antenatal visits in low-risk pregnancies would increase the accuracy of SFH in identifying fetuses with birthweight \< 10th or \> 90th, when compared to SFH alone. This is an open label, investigator sponsored, two arms randomized controlled trial. Patients who satisfy all inclusion criteria, have no exclusion criteria, and have signed the written informed consent will be randomly assigned to screening of fetal growth abnormalities during routine antenatal appointments held by midwives according to SFH or SFH + POC-US-AC. Low risk pregnant women are interviewed by a midwife at 35-38 weeks' gestation, who also reviews their medical and obstetrical history, prenatal labs and the ultrasound reports to discriminate between high and low-risk pregnancies. Patients who satisfy all inclusion criteria and do not have any exclusion criteria will be randomly assigned to one of two different approaches to identify fetal growth abnormalities and predict abnormal birthweight, after signing the written informed consent. Screening test in the control group: Symphysis fundal height measurement. Fundal height is measured by trained midwives at each scheduled antenatal appointment from the pubis symphysis to the top of the uterine fundus, using a paper measuring tape in centimeters. Size greater than dates is suspected if the measurement is above the 90th gestational age specific percentile according to the Intergrowth 21 SFH references (Papageorghiu 2016). Similarly, size less than dates is recorded if the measurement is below the 10th percentile for age according to the Intergrowth 21 SFH references (Papageorghiu 2016). Formal obstetric ultrasound is requested if the SFH is \> 90th percentile, if it is \< 10th , or if it drops 50 growth centiles in two subsequent evaluations. Screening test in the intervention group: Symphysis fundal height measurement + point of care ultrasound. After assessing SFH at each clinical encounter, the midwife will perform a POC-US to measure the fetal AC and evaluate the quantity of amniotic fluid. A positive screen for fetal growth restriction (indicative of a potential SGA infant) consists in a measured AC less than the 10th percentile for gestational age according to the standards defined by Nicolini et al in 1986 on an Italian population; instead, a positive screen for macrosomia (suggestive of a potential LGA infant) is an AC greater than the 90th percentile for gestational age according to the references set by Nicolini et al in 1996. Formal obstetric ultrasound is requested if the AC is \> 90th percentile, if it is \< 10th, or if it drops 50 growth centiles in two subsequent evaluations. Amniotic fluid volume will be evaluated determining the deepest vertical pocket (DVP). A formal US is requested in case uterine size is measured as ≤ than the 10th or ≥ than the 90th percentile for gestational age according to Intergrowth 21, when POC - US reveals AC \< 10th percentile, AC \> 90th percentile according to Nicolini et al, in case DVP \< 2 x 1 cm, or DVP \> 8 x 1 cm, or also if SFH or AC drop \> 50 percentiles comparing two subsequent evaluations. Patients randomized to SFH + POC-US will have a formal US if either technique suspects abnormal fetal growth. Formal US requested due to an abnormal screening test will be distinguished from scans ordered due to other indications, such as hypertensive disorders of pregnancy, or cholestasis of pregnancy diagnosed after enrollment. Hadlock' s references will be used to estimate fetal weight, and therefore to define FGR (i.e estimated fetal weight or AC \< 10th percentile) as well as macrosomia (i.e estimated fetal weight or AC \> 90th percentile). Prenatal evaluation of fetal growth will be compared to the birthweight percentile according to the INeS neonatal charts (Bertino 2010) to identify SGA, LGA and AGA (appropriate for gestational age) infants. After the initial evaluation low risk pregnancies are scheduled for antenatal appointments with a midwife at 40, 41 and 41+ weeks' gestation. All patients will have a POC-US by a midwife at 41, and 41+ weeks' gestation to screen for amniotic fluid abnormalities associated with protracted pregnancy, independently of the randomization arm. A midwife will perform SFH or SFH + POCT-US (according to randomization) at enrolment (35-38 weeks' gestation) and at 40 weeks. As sonographic assessment of fetal growth should not be performed more frequently than every 2 weeks due to the error associated with measurements; POC-US will only evaluate amniotic fluid volume at 41 and 41+3 weeks' gestation (unless the patient has missed a previous appointment), even among women randomized to SFH + POC-US. The purpose of the study is to evaluate the most accurate approach to identify prenatally those pregnancies that will result in SGA or LGA infants. Prenatal evaluation consists in a universal screening test for fetal growth abnormalities (either SFH or SFH + POC US) followed by a confirmatory test (formal obstetric US) performed only when the initial screening test is positive. Fetal growth or amniotic fluid abnormalities are diagnosed in utero if confirmed by a formal obstetric ultrasound, and not when only suspected by a screening test; in fact, the study seeks to evaluate what is the most accurate combination of screening and confirmatory tests, and not the effectiveness of the screening test alone.

Fetal Growth Restriction (FGR) denotes the inability of fetal growth to attain its inherent genetic potential due to diverse pathological influences. It stands as a significant determinant of morbidity and mortality during the perinatal phase, intricately linked with adverse long-term consequences. The etiology of FGR is complex, involving maternal, placental/umbilical, and fetal factors. Among these, maternal vascular malperfusion-related FGR (MVM-FGR) emerges as the prevalent subtype, which is considered to have potential for early intervention and prevention. To address this, we will establish a cohort dedicated to MVM-FGR, guided by a stringent diagnostic standard process tailored for FGR. Our objective is to compile a comprehensive dataset of singleton pregnancies diagnosed with MVM-FGR cases through multicenter collaboration. The definition of FGR aligns with the FIGO consensus criteria. We conduct thorough prenatal screenings for fetal factors, including genetic abnormalities, infections, and structural anomalies, subsequently enrolling MVM-FGR cases into our cohort. Techniques including Doppler ultrasound, magnetic resonance imaging (MRI), and electronic fetal heart monitoring will be employed to assess fetal conditions. Follow-up continues until the child reaches the age of two years postpartum. Pathological examination of the placenta is performed after delivery, with additional placental genetic testing if necessary.

Investigators are using a pseudo randomized yoked design and will include two groups: choice of intervention strategy or no-choice. If the individual is randomized to no choice, then the next person would get a choice and the no choice person would be assigned to the group yoked (matched) to the person with a choice. Participants assigned to the choice group will choose one of three intervention strategies provided; either Group A (receiving both nutrition and exercise simultaneously), B (starting with nutrition and receiving exercise sequentially followed by nutrition starting at 25 weeks) or C (starting with nutrition first and then introducing exercise sequentially at 25 weeks). All groups will follow the full NELIP until delivery. Participants in the no-choice group will be yoked (matched) to a participant in the choice group and receive the strategy that their yoked counterparts chose. Nutrition component of NELIP: This component is a modified gestational diabetic meal plan that has four general goals tailored to the participant: (1) to achieve approximately 2000 kcal of energy per day. The determination of the amount of kcal consumed per day will consider the participant's intake from the dietary assessment. There also must not be a restriction of calories that exceeds 30% of their total energy intake; (2) participants will consume approximately 200-250g/day of carbohydrates, accounting for approximately 40-55% of total energy intake. Carbohydrate intake will be distributed throughout three meals and four snacks daily. The nutritionist will educate participants about the importance of complex and low-glycemic index carbohydrates through the one-on-one session; (3) fat and protein intake will be approximately 30% and 20-30% of total energy intake, respectively; (4) achieve appropriate micronutrient and fluid intake for pregnancy. This will be monitored by a weekly 24 hour food intake record. Exercise component of NELIP: This is a walking program that comprises of 1 weekly supervised session on a treadmill or outside and participants will be recommended to walk 2 to 3 additional times per week. The walking program will start at 25 minutes per session, 3 to 4 times weekly, and increase by 2 minutes per week until 40 minutes and then maintained until delivery. This will be monitored by a wrist monitoring device. The primary outcome is adherence measured weekly using a published adherence protocol using a point system. Secondary outcomes are participant satisfaction to the program and health outcomes: weekly weight gain, calculated EGWG, and pregnancy outcomes (birth weight length, infant anthropometrics, APGAR scores and delivery complications). At 2, 6 and 12 months of age the maternal-infant dyad will return to the lab and infant morphometric measurements recorded from birth will be repeated.

The objective of this study is to evaluate the benefit of Karl Storz curved (11508AAK) and straight (11506AAK) fetoscopes for in-utero surgery. The investigators will assess the surgical outcomes, short and long-term morbidity, complications, and gestational age of participants who undergo intrauterine procedures with these devices. The scopes will be used to assist in intrauterine procedures across a variety of fetal conditions, such as TTTS (twin-twin transfusion syndrome), TAPS (twin anemia polycythemia sequence), sFGR (selective fetal growth restriction) or TRAP sequence (twin reversed arterial perfusion). Fetoscopic laser photocoagulation (FLP) can also be used during in-utero surgery to correct abnormal vessels in cases like chorioangioma or vasa previa. Other complex congenital anomalies may require fetal intervention or diagnostic fetoscopy using Storz scopes. Improvements in the technique, experience and equipment have been associated with better maternal, fetal, and neonatal outcomes in fetal surgery. Smaller fetoscopes are associated with lower rates of premature delivery following FLP. New fetoscopes (11508AAK and 11506AAK) have the potential to improve visualization and the photocoagulation angle. Compared to alternative scopes, these Storz scopes provide a wider angle of view and are longer, enabling better reach to distant areas at the edge of the placenta, especially in cases of higher BMI, higher gestational age, and significant polyhydramnios. This study is an un-blinded, non-randomized, single arm, feasibility study on a convenience cohort to demonstrate the role of a curved fetoscope device (11508AAK) or straight fetoscope device (11506AAK) among in-utero surgeries. Patients will be enrolled in a consecutive manner and all qualifying, patients who agreed to the use of the curved or straight fetoscopes will be enrolled in the study. Outcome data will be reported as a descriptive statistical analysis. The curved fetoscope (11508AAK) device will be used in monochorionic pregnancies with an anterior placenta requiring in-utero surgery, while the straight fetoscope (11506AAK) will be used in monochorionic pregnancies with a posterior placenta. This device is classified as a significant risk device because it is of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject.

DIP: Individuals with gestational diabetes (GDM) during pregnancy have up to a 10-fold increased risk of developing of T2DM. Postpartum screening facilitates detection of impaired glucose tolerance and diabetes mellitus with the possibility for subsequent preventive and treatment interventions. The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) recommend screening individuals with GDM postpartum with a 75-g, 2-hour oral glucose tolerance test (OGTT) that includes a fasting blood glu-cose.4,6 This is historically performed at 4-12 weeks so that it will coincide with the timing of the typical postpartum visit. However, the rate of postpartum screening with the recommended method are low, as many individuals do not seek timely postpartum care-only a quarter to one half of individuals undergo diabetes screening in the first year postpartum. Multiple structural barriers exist for patients and healthcare providers to effectively complete postpartum diabetes screening via the current recommended method. An immediate postpartum OGTT has been proposed as an alternative to the current standard practice which is generally performed between 4-12 week postpartum OGTT at the routine postpartum visit. An immediate OGTT has comparable performance characteristics for detection of impaired glucose tolerance and diabetes compared with a 4-12 week postpartum OGTT. Follow up PP CARE: Postpartum adverse CVH is a critical public health problem and contributes to persistent and inequitable maternal health. Adverse cardiovascular health outcomes after delivery, including hypertension, dyslipidemia, diabetes, and obesity, are frequent and a major source of maternal morbidity and mortality. Ultimately, these conditions increase the risk of long-term cardiovascular disease which affects 60 million women in the United States (US). It represents the leading cause of death, contributing to 1 in 5 deaths in women in the US. Despite these epidemiologic associations, relatively less research exists on prevention, recognition and treatment of adverse CVH in high-risk postpartum women before the occurrence of clinical disease. Further, adverse CVH is more common among individuals who experience an adverse pregnancy outcome (APO), as well as adverse social determinants of health (SDOH), including self-identified minoritized race or ethnicity as a proxy for racism, low socioeconomic status, housing and food insecurity, and limited access to healthcare.

This trial is a pilot-scale, single institution randomized, placebo-controlled trial to assess the feasibility, acceptability, and efficacy of administering dapagliflozin for cardiovascular risk reduction in the postpartum period. The target population is patients at high risk of adverse cardiovascular outcomes within five years post-delivery. Eligible participants will be randomized to receive either: 1) dapagliflozin (10mg daily) for six months (DAPA group) or 2) an orally administered, daily placebo (Control group). The study hypothesizes: The dapagliflozin group will have higher cardiovascular risk reduction scores than the Control Group.

Subjects: SGA children from 6 months to 2 years old who meet the enrollment conditions shall be informed of the enrollment by the researcher and the subject's guardian, and the subject's guardian shall decide to participate in the test drug group or the control group. GH treatment group (n = 68): the subjects were given PEG-rhGH injection 0.2 mg / kg / week (initial dose), once a week, subcutaneously before going to bed for 104 weeks. Each follow-up, the researchers adjusted the dosage according to the IGF-1 results of the center and other individual conditions. Control group (n = 68): no treatment, only follow-up examination and growth and development related evaluation, and the follow-up time was 104 Week.

Pregnancy complications are increasing in the United States, and this is worse for Black patients, who are 3-4 times more likely to die from pregnancy than White patients. Pregnancy complications and deaths cause large physical, social, and financial burdens for patients and their families. Black patients who experience higher levels of institutional racism and discrimination from healthcare providers and institutions are more likely to have pregnancy complications, such as delivering a baby with low birthweight. Low birthweight (less than 5 pounds 9 ounces) is related to many short-term and long-term health problems for both baby and mother. The study, Accountability for Care through Undoing Racism and Equity for Moms (ACURE4Moms), aims to decrease pregnancy complications for all patients, but especially for Black patients, by decreasing institutional racism and bias in healthcare and improving community-based social support during pregnancy. The primary outcome will be to decrease low birthweight deliveries among Black women. The investigators will get information about low birthweight and other pregnancy outcomes from prenatal practice electronic healthcare records. A secondary outcome will be to decrease experiences with discrimination during prenatal care among Black patients; this information will be collected from an internet survey that will be completed at 4 time points between a patient's first prenatal visit and 3 months after delivery. To meet the study aims, the investigators will test 2 types of interventions. The first type (the "Data Accountability and Transparency interventions") will be focused on healthcare providers and their clinics. The study will improve accountability by setting up electronic Maternal Warning Systems to notify the clinics whenever a patient has a risk factor for low birthweight that needs to be treated or misses a scheduled appointment. Provider champions from each clinic will make sure the clinic acts on the warning. Secondly, the study will improve transparency by showing the clinics their pregnancy-related complication data for different racial groups every 3 months through a "Disparities Dashboard." This Dashboard will show the providers any differences in pregnancy complications for people of different races in their clinic and encourage them to come up with ways to improve the quality of their care to decrease those differences. The study will hire "Practice Facilitators" to help the clinics improve their workflows and communication with patients. Finally, all the staff at the clinics will undergo interactive racial equity training to help them recognize any implicit biases they have and understand how racism affects pregnancy care for patients of color. The second type of interventions will be focused on improving community-level support for high-risk pregnant patients. The study will do this by matching community-based doulas who are trained to provide culturally-relevant care with high-risk patients after their first prenatal appointment. The doulas will then provide support to these patients during pregnancy with up to 4 visits during the prenatal period, supporting them for up to 24 hours during labor, and performing 1-2 postpartum home visits. The doulas may provide additional services during pregnancy and labor, and through peer support groups lasting up to 1 year after birth (the "Community-Based Doula Support interventions"). To test how these each of these interventions improves low birthweight alone and when combined together, the study has enrolled 39 prenatal practices across North Carolina, into 1 of 4 randomized arms: 1) No interventions; 2) Data Accountability and Transparency interventions; 3) Community-Based Doula Support interventions; or 4) Both the Data Accountability and Transparency and Community-Based Doula Support interventions. The investigators predict that up to 60,000 patients will start prenatal care at one of the 39 practices during the study. For the patient surveys, the study plans to enroll patients who self-identify as Black or African American from each of the 39 practices, for a total of up to 4,400 survey participants. The investigators will also interview at least 250 practice staff, doulas, patients, and Practice Facilitators to understand how well the study interventions fit their needs. The study is led by a Stakeholder Advisory Board, which includes patients of color who have had a pregnancy complication, community doulas, practice representatives, health insurance payers, a patient advocacy group, healthcare organizations, and the North Carolina Department of Public Health. The majority of members will be people of color. The Board will meet every 3 months throughout the study to advise us about patient-centered outcomes, assist with dissemination of results, and advocate for related policy change.

Zimbabwe's HIV prevalence rate is among the highest globally, and cisgender women of reproductive age are disproportionately affected. Considering the increased risk of HIV acquisition and transmission during pregnancy, there is an urgent public health need to develop interventions that increase the use of efficacious HIV prevention strategies like PrEP in the antenatal context. Oral pre-exposure prophylaxis (PrEP) is safe during pregnancy, effective in preventing HIV, and available in Zimbabwean antenatal care (ANC) clinics. However, PrEP use remains low among cisgender women of reproductive age. Individual-, interpersonal/community-, and provider-level barriers (e.g., psychological distress, stigma, low partner support, limited PrEP knowledge in providers) compromise use. A multi-level, problem-solving intervention that addresses barriers to PrEP adherence and persistence during pregnancy and through the postpartum transition among patients, their partners, and antenatal care providers could improve the health of pregnant persons, ultimately decreasing HIV incidence in Zimbabwe. The aims of this study are as follows: Aim 1: Explore the impact of intersecting, multi-level barriers on PrEP uptake, adherence, and persistence during pregnancy (n=30), and explore barriers to PrEP provision among antenatal care providers (8-10). In individual interviews with HIV-negative pregnant women with psychological distress (15 PrEP naïve, 15 PrEP experienced), the investigators will probe individual, interpersonal/community, and structural barriers/facilitators. It is anticipated that barriers to uptake, adherence, and persistence may include distress linked to common mental health challenges (e.g., depressed mood, posttraumatic stress) at the individual level; lack of support from partners and providers, stigma, and low PrEP awareness at the interpersonal/community level; and limited access to PrEP care and food insecurity/poverty at the structural level. Among providers, interviews will explore PrEP knowledge, perspectives on HIV prevention during pregnancy, and barriers to prescribing PrEP. Aim 2: Specify the manual and conduct a small proof-of-concept trial with patients (n=5), their partners (n=5), and providers (n=2). The new manual will teach skills to navigate resources and problem solve the multi-level barriers to PrEP use identified in Aim 1 and will include a group-based training for all providers (education on PrEP during pregnancy, negative PrEP attitudes/stigma, and other barriers to prescribing). Content of the manual will be interactively refined on five participants, their partners, and two providers. Aim 3a: Evaluate the feasibility and acceptability of the patient-level intervention in a pilot RCT (n=70). PrEP eligible pregnant persons with motivation to initiate PrEP who are experiencing psychological distress will be randomized to either the intervention or to enhanced treatment as usual (mental health referral). Primary outcomes will be feasibility and acceptability; it is hypothesized that the intervention (\~4-5 sessions, including one dyadic session with a partner, plus a postpartum booster) will be both feasible and acceptable. Aim 3b: Evaluate the feasibility and acceptability of the provider training (\~2 sessions), which will be offered to all providers (n\~10) in a nonrandomized design; it is hypothesized that the training will be feasible and acceptable. Aim 3c: Explore perceptions of key implementation outcomes among providers and other administrators (n=15) through individual qualitative exit interviews.

The overarching objective is to determine whether initiation of Kangaroo Mother Care (KMC) at the neonatal intensive care unit (NICU) followed by admission to the KMC ward for continued support for more than 2 days before discharge home reduces maternal postpartum depression (PPD) and other maternal and infant adverse outcomes in low-resource settings. The central hypothesis is that NICU KMC plus admission of mother-infant (preterm) dyads to the KMC ward following NICU discharge for more than 2 days will reduce the risk of maternal PPD as compared to NICU KMC followed by admission of the mother-infant dyad to the KMC ward for up to 2 days only. The study aims are: Aim 1: To determine the effect of admission of mother-infant dyads to the KMC Ward following NICU for more than 2 days on maternal PPD at 2 weeks, 6-8 weeks, 6 months, and 12 months. Aim 2: To determine the effect of admission of mother-infant dyads to the KMC Ward for more than 2 days on infants' developmental outcomes at 6-,12-, and 18 months of age. Aim 3: To characterize the feasibility and barriers to uptake of KMC at the hospital and following discharge from the perspective of parents and other family members. Aim 4: To determine the prevalence of paternal depression. Aim 5: To estimate the cost and effectiveness of admission of low birthweight infants to the KMC ward. Study design This study is a randomized controlled trial of newly delivered women whose preterm newborns have been admitted to the neonatal intensive care unit (NICU) with admission to the Kangaroo Mother Care (KMC) ward for up to 2 days (control) or with admission to the KMC ward for more than 2 days (intervention) prior to discharge home. The study will enroll a total of 1908 study participants from both study arms pulled from 612 mothers (aim #1), 612 infants (aim #2), 72 participants for in-depth interviews (aim #3), and 612 fathers (aim #4).