Chapters Transcript Video Health in Pregnancy and Impacts on Childhood Development This morning. I have the pleasure for introducing our speaker, Doctor Kimberly Lee Larson, who will be presenting on the impact that maternal health during pregnancy has on childhood development. Doctor Larson serves as a B CHO IC N division chief and as the co-director of the BC H Oak Fetal Treatment Center. She also serves as the IC N medical director at San Ramon Regional Medical Center. Doctor Larson received her B A in Psychology from Boston College, her medical degree from Drexel University and then completed her pediatric residency at Children's National in Washington DC. She then completed her fellowship in neonatal perinatal medicine at Rainbow Babies and Children's Hospital in Cleveland, Ohio. Please join me in welcoming Doctor Larson. Thank you, everyone. Thanks so much for having me. Um So for today, so again, uh we'll be talking about health and pregnancy and the impacts on childhood development. Um This is a pretty big topic. So we're gonna break down how we'll go through this um and hopefully make this uh engaging and um have some kind of high level points for everyone. Um So I already got the introduction there, but a little bit more about our fetal treatment centers. So, um so one of my main roles is to serve as a neonatologist at Children's Oakland. And I also work at some of the community level threes as well. And in the fetal treatment center, for those who aren't aware of it, we have this multidisciplinary clinic. So it's here in the outpatient center and we're led by a maternal fetal medicine specialist. So it's an ob who has um specialized in high risk pregnancies as neonatologist. And then uh many of our different pediatric subspecialists depending on the needs of the family. So families come to us for fetal imaging. We do ultrasound MRI and echoes amniocentesis and consultation with the many specialists. Um We also have genetic counselors and social workers as well. Um And so our goal is to provide guidance to families on delivery plans of postnatal care and of course, uh work with our pediatricians as well as we carry those plans forward. So, the objectives which were included when um we sent out the CME about the session are here. Um And so we'll review important preconception guidance for optimal health and pregnancy. And childbirth, discussed the more common maternal conditions in pregnancy and their influence on fetal and neonatal health and long term childhood health. And we'll explore some of the more common fetal conditions in pregnancy which may be encountered by primary care pediatricians and some renal cns findings and respiratory complications. And some of the follow up and long term outcomes. So how we will do this. Um So essentially, the way I thought about this talk is if I were spending a day in our, our fetal treatment center, um what would I consider some of the more common things I would see? Um And how might that be helpful to, to you all as an audience? So, we'll talk a little bit about preconception guidance and I know this is probably the, the area that we're all a little bit furthest from. But still important to think about as we work with families as a whole, we'll talk about pregnancy, um specifically for maternal conditions, hypertensive conditions, diabetes and nutrition. We'll talk a little bit about some placental conditions that are more common and cause uh more impact for the fetus and neonate. And then for fetal, we'll talk about growth restriction and then hydronephrosis and ventricular megaly as two of the more common issues we see and then transition into neonatal and childhood. And the reason I group this together is that many of the conditions we'll talk about in pregnancy can lead to preterm birth, early term birth and growth restrictions. So that's why we'll group all of that together as we talk about um once the baby is born. So let's start with some questions. So short interval, pregnancy increases risk of low birth weight in the neonate, increased risk of preterm birth is commonly defined as birth to conception of less than 18 months, all of the above or none of the above. And it's a little harder when we're on zoom if anyone wants to speak up, but um I will just move through them. So all of the above are true and we'll talk about this in more detail. Symmetric growth restriction often occurs later in pregnancy and is often associated with uteral placental insufficiency, true or false and this is false. This is describing asymmetric growth restriction. Children impacted by fetal growth restriction have an increased risk of cerebral palsy. Most commonly retain a low weight through it. Uh for age throughout childhood have similar neurodevelopmental outcomes to non IUGR Children have brain volume differences at birth that most often resolve in childhood. This is a when mild fetal ventricule megaly is present with no additional risk factors or findings on imaging or genetic and infectious studies. The vast majority of Children will have favorable neurodevelopmental outcomes. This is true when compared to pregnancies without diabetes. The risk of birth defects is highest in pregnancies impacted by gestational diabetes. Type one diabetes, type two diabetes, B and C are all of the above. This question probably wouldn't make it on the boards because you could probably argue a couple of them B and C is probably the best answer and we'll talk a little bit more about why. So starting with preconception care. So, pre-existing conditions. So kind of thinking through um not that pregnancy is a prior pre-existing condition but short interval pregnancy. So this is defined most commonly as 18 months. There is a little bit of variation out there. But um generally, that's meaning from the, the date of birth to the the prior child to the date of conception for the next pregnancy. Um, so we're looking at Children that are in age far, far more space than two years apart. Shortage of pregnancy has been associated with an increased risk of low birth weight, low apgar score being small for gestational age and preterm birth. And one of the big reminders here that will be a theme throughout the talk is this um to remember that organogenesis in the fetus is complete before week nine of gestation or seven weeks after conception. So, in preparing for pregnancy, we wanna think through managing pre-existing conditions for those with diabetes, good glycemic control is very important, which we'll get into more detail on for hypertension. You wanna continue to treat and keep good control as you can. But transition to medications that are better understood in pregnancy, generally avoiding ace inhibitors or sper lactone depression anxiety. We absolutely want to continue to treat to begin counseling regarding um pregnancy and postpartum risks and understand that SSRIS are some of the best studied in pregnancy. Though most of our medications uh could use some better studying and then think about supplements like prenatal vitamins that are having higher levels of folic acid and iron and of course, as every area of medicine um encouraging nutrition and exercise. So, nutrition before pregnancy, during lactation can impact long term childhood health. And there's this idea of developmental origins of health and disease. So there's an um a early nutrition project which is um throughout the world. Actually, there's uh Europe in, in, in the States in Australia. And so this is a multidisciplinary research collaboration that explores how nutrition and metabolism during sensitive periods of early developmental plasticity can have an impact on cytogen, organogenesis, metabolic and endocrine responses as well as epigenetic modification of gene expression, thereby modulating later health. And I took this directly from their paper because it was worded so nicely. Um But essentially looking at preconception as an essential time point to impact later health. Um And an example given which I think is helpful is that, you know, obesity and pregnancy has a significant impact on maternal and fetal health. And we know this, however, dietary and medication interventions in pregnancy um really don't have a large impact on decreasing those risks which again points us towards preconception counseling and thinking about that time period. So entering pregnancy, physically healthy, um physically active with a healthy BM I avoiding smoking, alcohol supports pregnancy health. And again, these um extra supplements, uh unintended pregnancy. So when a pregnancy is not planned, accounts for almost half of pregnancies in the US, it overall seems to be declining, but it does remain highest in our highest risk groups. Um There's been many analysis looking at studies um about the impact of unintended pregnancy. Um seeing an increased signal towards increased uh maternal depression and maternal violence, increased uh preterm birth and included the odds ratios for this and for low birth weight, they're not huge, but there is definitely a signal in that direction and it's important to be aware of. So when we look at the healthy people, 2030 goals, there are quite a few related to this topic. Um So goal to reduce unintended pregnancy as it's linked to preterm, birth and postpartum depression interventions to increase use of birth control are critical for preventing unintended pregnancy. Birth control and family planning services can also help increase the length of time between pregnancies which can improve health for women and their infants. And when you go in a little bit further on the healthy people, 2030 site, um I found this just interesting and helpful for some of the pregnancy and childbirth topics as well as family planning. Um but also a little bit disheartening for some of the topics. Um and you may all be aware. So in terms of the the goals to reduce preterm birth, we are heading in the wrong direction. So 10% and then increasing closer to 11. Um we're attempting to increase the proportion of pregnant women who receive early and adequate prenatal care. This is getting worse as well. Um And same with women who had a healthy weight prior to pregnancy. I'm gonna move over to pregnancy now. So we can get in a little bit more on some of the more common conditions and, uh, the way in which these will impact the, the fetus and neonate. Um, and one thing I will mention, um, Doctor Kinsey gave a talk, um, just a couple of years ago, kind of going into a lot of detail about maternal conditions and treatment and some of the specific medications. Um I won't go into quite that depth so that we can um transition over to talk more about some of the neonatal time period and the um the childhood outcomes. Um but in thinking of hypertension, so this is um present up to 10% for all hypertensive conditions um worldwide and it's increasing. Um it's the most common cause of maternal deaths worldwide. Developed countries um have uh less mortality than developing countries where mortality can reach up to 20 to 30%. And there's higher risk in the African American women as compared to Hispanic Native American Asian Pacific, Islander and Caucasian. So when we think about the changes that are occurring during pregnancy, so in general, increased heart rate, blood volume and cardiac output, but decreased blood pressure. And so there's this um kind of flow that happens where blood pressure decreases early on levels out about midway through pregnancy and then returns to the patient's baseline towards the end of pregnancy. So when we think about definitions for how we would um look at different types of hypertension experienced before or during pregnancy if there's increased blood pressure, noted before 20 weeks, cessation, that's more likely chronic hypertension if it's diagnosed week 20 or after and is new to this particular patient, that's gestational hypertension. And then when you have hypertension with proton Nuria or significant end organ dysfunction, that's when we get into preeclampsia, which is a specifically pregnancy related condition. And you see a list here of some of the specific risk factors that make a patient at higher risk for hypertension. So in terms of then the impact on the fetus, um we think about the vascular changes and the uteral placental insufficiency, which can then impair oxygen and nutrient delivery. There is a higher risk of intrauterine fetal demise. This is higher in developing countries. There is an increased risk for fetal growth, restriction, preterm birth for placental abruption, which can then confer risk for low apgar score and risk of asphyxia to the immune and overall a higher risk for nicu admission, moving over to diabetes. And so, thinking of one of our other more common conditions that are faced that is faced in pregnancy. One of the big points again, kind of linking back to us talking about um the early parts of pregnancy and organogenesis is pre gestational versus gestational diabetes. And there's a difference in the fetal risks based on the timing of the exposure to hyperglycemia. So, we're looking at a 1 to 2% for pre gestational diabetes and 6 to 9% for gestational diabetes. So, pre gestational diabetes confers an increased risk for birth defects because of the high sugar. During the early parts of pregnancy and organogenesis. The risk of defects increases proportionally with the glucose levels. Hyperglycemia has been linked to oxidative stress, cellular apoptosis and an altered gene expression. Good glycemic control improves the risk, but it hasn't quite been able to decline the risk to what the general population experiences. So, about 3 to 18% versus 2 to 3% for birth defects. And we don't quite know what an optimal hemoglobin A one C is in terms of the congenital malformations and in birth defects, there's quite a long list. Um The most common things we'll see will be congenital heart disease and C MS defects. Um You can see a long list here. The kind of next big category that we often think about. Um and especially in kind of about the way to put the picture together for the infant of a diabetic mother would be some of the G I differences. Um Du Adonal tria interpreting this small left colon. We can see gu differences um and musculoskeletal abnormalities, c palate, single umbilical artery. Um A note here on caudal regression syndrome. So, in general, this is a very, very rare finding and however, it is almost uniquely linked to patients with diabetes or poor glycemic control. There are very small numbers of cases in women who truly had no issues with their blood sugar but does seem to really be linked to it. And this is a developmental anomaly with um a variety of severity but essentially a um a regression kind of to the lower part of the spine down to the extremities. So there are not a lot of studies that look at type one and type two diabetes separately. But there was a larger population study done more recently, which looked at about 700,000 pregnancies. Um and what they decided to do was separate out by insulin use, knowing that insulin generally increases overall risks in pregnancy. So for maternal diabetes requiring insulin in their study, about 37% of the babies are born preterm, 40% large for gestational age. And they focused in just specifically on these two factors. When they looked at patients with type two diabetes not requiring insulin, it was about 10% preterm, 13% large for gestational age. When they looked at gestational diabetes with no insulin, it was 5% preterm, 5% large for gestational age and then no diabetes, 5% preterm and about 2% being large for gestational age. So the other issues we see are that maternal hyperglycemia throughout pregnancy leads to fetal fetal hyperglycemia and hyperinsulinism. The insulin itself impacts growth and development through all organs, especially the heart and liver and the overall growth of the fetus. So we can see macrosomia, cardiac septal hypertrophy um and some metabolic changes that we'll discuss when we switch over to talk more about the neonate. Um I liked this uh when I was looking through some of the resources, this is a pretty recent study and I liked that they provided this visual abstract. Um I am definitely a visual learner. So um helpful for me. So I thought I would just share this rather than trying to, to make a list of some of the findings here. But and this particular uh meta analysis was looking specifically at gestational diabetes. And again, their goal was to look in at no insulin use and insulin use, looking at some of the maternal outcomes and neo out neonatal outcomes. And when you look at the forest plots here and looking at the shift towards higher incident for some of these things for um patients who experience diabetes with a little bit more of a shift related to insulin use. Um So some of the things that uh we are focusing in on here. So preterm delivery, certainly seeing a signal in that direction R DS uh respiratory stress syndrome, which we'll talk about a little more when we talk about the babies. Um low apgar score, macrosomia being large or small for gestational age, actually. Um low birth weight uh with insulin is actually a little bit on the other side, which is not surprising with insulin as a growth factor. Um and general admission to the neonatal IC U higher. I'm gonna shift over here from the, the two kind of main pregnancy conditions to uh or maternal conditions, I should say to placental conditions. Uh And these are some of the conditions that are not commonly seen, but I would say for us, um in the FTC, we see a bit more commonly. Um And just a reminder because I think for many, you probably haven't gone through this um since ob rotations, but just thinking through kind of the way in which some of these conditions might be risky for the, the neonate. Um So abnormal presentation. So we'll actually start with vasa previa. So vasa pre previa and placenta previa are separate and different. Although um they can occur in conjunction with one another or as a placenta, previa is resolving. So a vasa previa actually refers to fetal vessels passing over the cervical gloss. So this is the top picture up here with the, the baby in it. And the most common type is type one, which is about 90% in what you see in the picture. So you have the placenta, you have the fetal vessels, vessels coursing over the cervix and then attaching into the cord. And the problem here by the photo is I I think um evident in that then you have unprotected fetal vessels that are blocking the the baby's exit essentially. Um type two is a little bit different. You have a bi lobed placenta. So there's a piece on either side with the fetal vessels in between uh placenta previa, which is much more common refers to the position of the placental in relation to the cervical os um being close by. So with these pictures over on um the right side of your screen, we see in a, a normal placenta, um we see in va low lying placenta and then see a placenta previa actually covering the cervical os and then morbidly adherent placenta or the placenta accreta spectrum refers to, then a placenta that is actually invading into the uterus itself to varying degrees. So an accreta adhering to the myometrium, an increa invasion invading into the myometrium and per creta invading into the cirrhosis of the uterus. Um And as you can imagine, this presents a lot of risk both to the neonate and to the um the mother as well. So any of these conditions can impact fetal size and growth. Um anything where there's abnormalities and presentation can impact the nutrient delivery to the fetus. And as you can realize, you need C section delivery. So this means that there's a lack of labor and preterm delivery. And there was a 2015 study looking at delivery before 37 weeks related to some of these conditions. So a low lying placenta about a quarter of the time uh previa approaching a half accreta, more than a half Basa Previa for most of the um the neonates in the study. Um And then the table over here on the right is actually just to highlight this is a very rare condition for Besa previa. Um However, a very serious condition and with the advent of improved ultrasound technology, one that we fortunately are picking up ahead of time much more often now and able to prepare for. Um but seeing that um needing ac section is much higher uh or is 100% but needing an elective C section in this particular study was about 70% of cases, an emergency section in about a quarter of cases. Um postpartum hemorrhage having a higher signal admission to the NICU. Um We'll talk about why that admission to the NICU is 100%. Um Giving you an idea here with the length of stay in the NICU probably related to prematurity and then need for blood transfusion. Um and neonatal death being a little bit of a higher signal, although very small numbers overall. So then kind of moving into fetal conditions and thinking about growth restriction, which um is unfortunately quite common in pregnancy. So FGR or fetal growth restriction is essentially the inability to reach individual growth potential. And it's a challenging area because there's multiple definitions that exist. And fetal growth restriction is not the same as small for gestational age. You may have a baby that's imp impact impacted by fetal growth restriction, who could be a G A average for educational age and not all small f educational age babies were impacted by fetal growth restriction. As we well know there when we think about our growth curves and we expect everybody to fall somewhere along a growth curve. So we may just have individuals who are constitutionally smaller um but not actually impacted by fetal growth restriction. The reason this is important is because of some of the additional risks that come from actually being growth restricted or nutrient deficient. Um So worldwide, this is about impacting about 10% of pregnancies. However, in the world of neonatology, this is impacting quite a lot of our babies who were born extremely preterm. Um Fetal growth restriction is increasing and related to infertility treatments, multiple pregnancies, older motherhood stress, nicotine malnutrition. So, fetal morbidities are directly related to the gestational age at onset of birth restriction, the severity of the restriction and the etiology. So early versus late looking at before or after 32 weeks, gestational age and ideologies are broad thinking about genetic placental, maternal or fetal conditions that could cause this asymmetric versus symmetric growth restrictions. So the way I generally think about this is if there is something inherent to the fetus that is causing the growth restriction, um a genetic condition and infectious cause more likely it's going to be a symmetric growth restriction if it's related to the conditions of the womb and the placenta, it's more likely going to be asymmetric. Um when presented with the nutrient deficiency, the body will prioritize brain growth. Um And so, up to 80% of fetal growth restriction is asymmetric and kind of goes. Um links in with some of these other topics we've been discussing and this is what we'll focus on. So, fetal growth restriction itself confers risk for fetal morbidity, stillbirth, neonatal morbidity and mortality. There is an impact on fetal lung development. Um and just as a quick plug in kind of to tie things in. Um Doctor Sandra, we will be talking to us at a coming session about bronchopulmonary dysplasia and the neonates. Um And this is certainly a big area that we think about for the risk for those babies. So I will, I will let her take that away. But um but knowing that there is some impact on the lung development, um and then the surveillance is essential for obstetricians and MFM providers to follow the fetal status, the risk of hypoxia and balancing the risk of preterm birth. And so where we find ourselves and I include us as the neonatologist, since we're often involved in counseling families is a balance between the health and growth of the fetus in utero with the risk that come inherently with preterm birth. Um And some of the more objective data that can help in thinking through these decisions um would be surveillance during pregnancy including growth scans. So typically, it will be provided with an EFW or an estimated fetal weight with multiple growth parameters, helping us put that together. Um from what our ob colleagues have shared often in the abdominal circumference is one of the more stronger predictors there. Um growth scans are often done every two weeks but not often, not more frequent than that. Um given lower yield umbilical dopplers, which are interesting in what I've included a picture here for. So, looking at the umbilical artery, this is sort of a surrogate marker for the placental health. Um So looking at the flow in diastole, which is particularly helpful and um for many residents who are admitting babies in the NICU, you often see these abbreviations like absent a edf, absent and diastolic flow, redf reverse and diastolic flow. And what this is showing you that is that your placenta, which is usually a low resistance circuit is starting to have changes in those pressures that's impacting the flow and diastole, um which is a poor uh prognostic factor and when we're thinking of the health of the pregnancy, um and the timing of delivery. So certainly getting to reverse and diastolic flow which you see in the third wave there um is being quite concerning um nonstress tests are done where there is monitoring for fetal contraction or for uterine contractions and fetal heart rate response. And then by a physical profile which gives us a better idea about fetal movements, fetal breathing, the amniotic fluid levels, um can also include a nonstress test. Um to give us a score, again, kind of giving a picture of the health of the pregnancy and thinking about timing for delivery. So for fetal developmental risks, so again, thinking of respiratory uh impact for nutritional hypoxia. Um interestingly, you know, at some point along the way, we actually thought that babies who faced growth restriction and stress um were more mature and that they sort of got a bump up. But we've been seeing lately that that's really not true. There's an impact on uh surfactant perion alveoli development and the overall lung architecture. Um blood is preferentially shunted to the brain. Um So this can impact other organs of the body and um immune function and an impact on cell lines. And we'll get into this a little bit more when we talk about the immune. This is a very busy picture, but I wanted to include it because I reference it frequently and I find it very helpful. Um So this is from a cod the American College of Obstetricians and gynecologists and from 2021 they essentially put together these charts that were done previously. The reason it's highlighted was for some changes. Um but just basically giving some reference guidance on um times when a medically indicated delivery before term is um is needed. So where some of this comes from is that um you may be aware that there was a movement really around, I think 2010 to 2015 to really push away from un indicated early term birth. So delivery before 39 weeks without medical reason and knowing that we were seeing that really babies 3738 weeks, they are different and they don't have the same maturity as babies born 39 weeks and after. Um and so this provides some guidance for cases when you do have a medical indication, what might be the optimal window for delivery. Um And what you'll see here is many of the conditions that we have been discussing are on here. So up at the top, the placental and uterine conditions, um some of the fetal conditions specifically with growth restriction and it goes in here to look up at the um the artery dopplers as well to give some guidance and then hypertensive conditions and diabetes as well for um looking at particular uh risk factors in addition to just having the condition, um and some of the maternal um health factors as well. So, um as you can see for many of these categories, we are looking at delivery either in the late preterm period or the early term period. So these next two topics are gonna be a little bit different, but I wanted to include them since there's something that we see so frequently and I hope will be helpful to at least take a moment to touch on. Um So for fetal conditions, so specifically, just things that we're seeing when we're doing the initial anatomy scan for a fetus. Um One of the more common is to see hydronephrosis. Um So about 1 to 5% of pregnancies will see this. Um and does seem to be increasing, which may be related to increased imaging. There are many different causes that can happen. So it could be genetic causes impairment or renal development or fetal injury. And to make things complicated, there's a few different grading systems that are used. So, um just to make you aware of them. So the renal pelvic diameter, the society of the fetal urology has a different system and then a urinary tract dilation. And there's some pictures here just giving you the different grades that you may see anywhere from grade one, the least severe, up to grade four, the most severe where you're seeing. Um not only dilation but thinning of the pereny and looking at the differences in if you're using the renal pelvic diameter for measurements in the 2nd and 3rd trimester, for how we would differentiate mild, moderate and severe for the second trimester, we're looking at seven millimeters from 7 to 10 to greater than 10 and then the third trimester at 99 to 15 or greater than 15. Um And so what's really helpful and important is that the majority of cases actually are not clinically significant and it's transient in about 50 to 70% of cases. And really our goal here is to identify the fetus and therefore the neonate child that's at risk for congenital anomalies of the kidney and urinary tract. And the way I often think of it is, it's actually in some ways, the way I think of the newborn screen, we want to um catch babies that we might not otherwise have, um, found this in until there was something like a urinary tract infection or a severe illness. Um And so you see some percentages here for some of the more common an atomic differences and when, um when we might see them in relation to seeing hydronephrosis. So, in terms of the fetal management, um if we have um a low risk, um, so mild dilation scene before 32 weeks, often there'll just be one more fetal ultrasound prior to delivery to check in and repeat the measurements. Um, when there's higher risk, they'll be monitoring more frequently and investigations for other morbidities. Um, rarely we're considering fetal intervention. Um when antenatal diagnosed the chance of resolving or improving does correlate with severity. So 98% of mild cases will either remain mild or will resolve completely. Um, a little bit less for moderate and and less likely for severe when we think about postnatal management. A couple of the take homes that are important, especially when we're providing our postnatal plans. Um, we often delay the first ultrasound because it can underestimate findings if it's done too early, low risk patients will actually wait until 3 to 4 weeks of age to do a renal ultrasound. And that will be done in conjunction with the um visit with either nephrology or urology. Whoever has met the family prior to delivery for high risk. We often want to have the scan done during the birth hospitalization. But after 48 hours with close interval follow up and in severe grades that may also include avoiding cystic urethra gram or ABC UG postal antibiotic, prophylaxis is generally reserved to more severe cases. And in most cases, we're choosing something like amoxicillin or cephalexin. And then just as a reminder, regardless for any of these conditions, it's extremely important to counsel the family about the risk of UT I and what that may look like and I neonate and when they should seek medical care, shifting over that to our other fetal topic that we see more commonly and ventricular megaly. So seen in about 1% of fetuses and the risk of this is increased in fetuses with other anomalies. Genetic conditions or congenital infections. When we think through different mechanisms for this, this can either be pereny loss than causing the ventricles to look bigger. Um obstruction, causing the ventricles to over distend or CS F, overproduction again, causing the ventricles to distend. So when we look at the measurements, you can see a picture up in the corner there. Um And this is a really nice article actually for the reference there that was kind of geared towards what do we tell parents when we find this? Um, and looking at measuring the distal lateral, the lateral ventricle and with a measuring an amount of 10 millimeters or greater, um, that's when you would define ventricular vly and kind of go down the path of more investigations. Um, there's a couple of different um definitions here. So for mild, um generally, some studies just do mild and severe and some will do mild, moderate and severe. So um mild, typically, either less than 15 millimeters or 10 to 12, um moderate when that is included 13 to 15 and severe, greater than equal to 15 to 16. So, in terms of the work up, we think they're doing genetic testing. Um Just a quick kind of note here. So things are, are changing quickly in terms of the, the routine um screening that's done for every pregnant individual. So N IP T or non invasive pregnancy testing also referred to a cell free fetal DNA, um is now actually done for all pregnant individuals and offered to all pregnant individuals. Um Previously, it was reserved for those of advanced maternal age. Um and this is where there's blood sampled from the mother and there is fetal DNA that is taken out fetal cells, um and then screened for some of them more um uh common genetic conditions. Like Trixy 21 1318. Um So noninvasive testing, certainly not diagnostic but uh available and readily available in California amniocentesis. Um this is more invasive but is diagnostic. So, a sample of the amniotic fluid is taken and that meant may then be said for karyotype micro ray in some cases, whole genome or whole exome sequencing um infectious studies. So in particular thinking of things like toxoplasmosis CMVHSV, checking for uh rubella immunity and then for imaging in addition to an ultrasound, uh we can think about doing a fetal MRI. And ultrasound is helpful for looking at things like the ventricles and doing measurements, but doesn't quite get the same uh degree of detail that we can get with a fetal MRI when thinking of other structural differences. And so the the picture here kind of gives, gives the lead here. But essentially, um when we think about outcome, when there are no other findings in this work up, um outcomes can be very good. So um just to cut back here. So for postnatal planning, um so what you may see as a pediatrician more often would be patients who have mild diagnosed. Um that being because if there is severe ventricular megaly or if there is quick progression of the ventriculomegaly, we will often recommend observation in the NICU um there's risk of apnea and this also facilitates further work up including postnatal MRI. And most often we will be recommending head ultrasound after delivery. And then again, if there are other findings, we may consider brain MRI as well. And so the outcome is very broad and related to having additional findings. But if there is again isolated ventricular megaly with no other imaging genetic or infectious findings, there are very favorable neural developmental outcomes and often mild are included together in studies. And and so, looking at a neurodevelopmental difference, diagnosed in less than 10% versus looking at severe cases where having a neuro neurodevelopmental normal neurodevelopmental outcome was less than 10%. Switching over now to looking at the neonate and through childhood. Um So again, kind of our big picture here is when we think about a lot of these more common pregnancy conditions, many of them then present a risk for preterm delivery. Um and many of them can cause growth restrictions. That's why we'll talk about these together and then just a little bit about the infant of the diabetic mother. So I'm thinking of preterm birth. So this is about 10% of all births. Um But importantly, especially for thinking of uh the outpatient setting, about three quarters of these babies are gonna be late preterm. Um So this is 34 and 0 to 36 and six. We then define early term as 37 and 0 to 38 and six. Overall, there's higher morbidity mortality related to those um being term at 39 and zero and some of these risks will increase related to maternal risks during the birth hospitalization. Some of the more common things we see would be hypothermia, hypoglycemia, respiratory stress, apnea, and jaundice. And practice varies throughout the country. But locally, the most often the practice kind of related to understanding these risks is that any baby born before 35 weeks will be admitted to the NICU with the plan to be discharged from the NICU and babies in the 35 week range will often have an observation period in the NICU or transitional nursery. And this is again hoping to discover those babies who may have some of these difficulties with hypoglycemia, temperature control, respiratory distress. Um And many babies at 36 weeks will we will intend for them to go to the nursery. But of course, uh many of them will come to us as well. And the A AP recommends against early discharge for late preterm neonates and recommends watching them for 48 hours or later. Um And part of this is because of the high rates of readmission. So about 5% in the first month. Um poor feeding, poor growth jaundiced. Um and um unexplained uh ethnic type events for preterm birth and any resident who's worked with me has probably been been tortured through looking at the lung development picture here. This is um one of the one of my favorite ones just because it makes a lot of sense to my brain. But um essentially, you know, we think about the important steps in lung development and as a neonatologist, really that, um, the little tick mark going along the 24 week mark is a very important one that we talk about a lot. Um, but then really thinking of the one at the 36 week mark as well, we're actually just getting into the alveolar stage. Um, and watching that little kind of curve of the surfactant production increasing. Um So just giving us uh giving babies credit for all the work they do late in pregnancy. Um And so the complications of the differences in lung development are also uh complicated by decreased fluid resorption. Higher instance of apnea and pulmonary hypertension. There was a population study looking at R DS and mechanical ventilation specifically for late preterm neonates um showing R DS and about 7% of those at 34 weeks, 4.5% of 35 and 2.3 at 36. Um And the mechanical ventilation actually needed about 6% of the 34 weekers, 3% of 35 and 2% of 36. Um We know that kind of thinking of um the big picture for lung health, there is higher risk for admission in later infancy and childhood. Um Most commonly this is related to respiratory illnesses. There's an increased risk in childhood for respiratory illnesses, but less clear for overall lung developmental differences. There's some that suggest that there may be differences in lung development. Um And I will say, you know, it puts us in a bit of a challenging position when we are talking to families. Um And often for me, when I think about it, we are in a situation where we don't have a choice about a baby being born early. Um And when we're thinking about balancing risks of remaining in utero, especially with some of these conditions like growth restriction or placental differences. Um This is what we're faced with. So I will often talking to families say, yes, we understand that there might be a bit of a difference here. Um But in the bigger picture, having a late preterm baby, we are not going to see a lot of differences in terms of the overall lung health and really overall development. Um And certainly we know that there's a lot of environmental factors that play into that. So recognition early and, and being able to link into things like PT and OT if needed. Um being extra vigilant in times of respiratory season and respiratory illnesses can really make a difference. Um There is a higher risk for infant mortality for those born preterm related to term. Um And the range here of the 2.5 to 6 times was comparing 36 down to 34 weeks. Um for neurodevelopment mental differences. Again, you know, for the most part, we, we are very positive in our counseling for families who are facing late preterm birth. Um but it is helpful to just remember um this, this image that you're seeing here and that the brain volume really at 36 weeks is quite different than that at full term. And the studies that are a bit mixed, so it's a little bit less clear, some show, you know, differences in neural development and some do not. And the specific areas concerned that we would always look into would be cognitive impairment, motor impairment, vision and hearing loss, and psychiatric and behavioral disorders. Um Shifting over to fetal growth restriction. I think I'm running a little over here. So um we know that there's a high risk of preterm birth in addition to being growth restricted. Um we can sometimes use the ponder all index which is essentially giving us a ratio of body weight to length, which is a increase um in impaired temperature regulation. There's an increased risk of perinatal asphyxia. Um This is related to some of the differences in placental function, difficult transitions during labor and difficult tolerance of labor as well related to that placental health. Um The specific things that we find for babies who are growth restricted. So there's an increased risk of respiratory distress at birth and BPD later on asthma and bronchiolitis, there's a risk for infection related to decrease in our immune cells. So, therefore, an increased risk for late onset sepsis. Some of the hematologic differences related to the fetal hypoxia. So, polycythemia increase included red cells and then can lead to a risk of hyperviscosity. Um the endocrine differences. So, decreased energy reserve in glycogen stores, as well as some hyperinsulinism can lead to hypoglycemia. Hypocalcemia is a little bit less understood but perhaps related to a decreased in transfer during pregnancy. And then what is um challenging and interesting is being growth restricted actually sets you up for um o obesity and conditions of obesity later in life. So, there have been a lot of studies looking at cardiovascular health, looking at metabolic syndrome and seeing that these are increased for those who experience growth restriction. I'm thinking that there may be some epigenetic factors at play there. Um There may be an impact on renal development which later would impact vascular changes. Um the metabolic syndrome. So seeing obesity, hypertension, dyslipidemia, insulin resistance. And um what's challenging is that for many babies born growth restricted, you'll see some catch up growth in the in infancy. Um But there may be a propensity to actually overshoot which can increase some of the risk and unfortunately, both poor growth um and excessive po postnatal growth can impact the risk. So, about 15% of babies that are born grow restricted will remain small throughout infancy. Um Grossly babies born growth restricted are at higher risk for neuro developmental impairments. Um and this risk does seem to persist after adjusting for some of the confounders like socio economic status and prematurity. Um The study is actually there's some concern that they may underestimate because often constitutionally small neonates may be included. And as we talked about um being constitutionally small is a different uh patio physiology or different physiology than the pathologic changes of being growth restricted. The exact mechanisms are not yet understood, but we think about fetal hy hypoxemia, malnutrition and stress. Um and then overall seeing decreased brain mass compared to neonates that were not IEGR. And then we'll move just quickly here through specific conditions related to being the infant of a diabetic mother. Um So we talked early on. So essentially your um your exposure to high sugar impacts the findings. So pre gestational diabetes, again, thinking more birth defects and then continued exposure to glucose throughout the pregnancy means that both gestational and pre gestational diabetes are at higher risk for things like macrosomia being large for gestational age, either birth weight more than 4 kg or being the nine percentile for gestational age. And the overall size of the baby is increased. There's increased fat mass, increased organ size, but not differences in brain size or growth. There's an increased risk for a preterm delivery. Um This can be medically indicated, there's not uh it's not quite clear if there is an increase in spontaneous preterm delivery. So, thinking back to that chart that we had with some of the reasons we may have a medically indicated birth before 39 weeks and there are delivery related risks related to being macrosomia. Um So asphyxia related to the delivery itself or to the intrauterine condition, he increased risk of shoulder dystocia. There's an increase in chest and shoulder size, disproportionately and increased injury related to to that with the delivery with brachial plexus injuries and fractures and the cardiac difference is this is always helpful for me to think through again, kind of remembering um the exposure time for the hyperglycemia. So we went through earlier kind of the long list of actual structural congenital heart disease. Um but a condition that can be faced by um infants of diabetic mothers, either pre gestational or gestational is actually more of a growth condition. So seeing um septal hypertrophy um and the difficulty with this is that you can get interventricular septal hypertrophy that can cause an obstructive picture. So, with higher heart rates causing the heart to under fill um in many cases, when we see this, it is not symptomatic to the baby. But in severe cases, we may be thinking of things like a beta blocker to slow the heart rate and allow for time for the remodeling to happen that happens after birth um for respiratory uh complications. So, respiratory distress and TT N and there's an increased risk there. Some of this may be related to timing and mode of delivery but R DS itself. So actual surfactant deficiency is increased in ID M babies related both to preterm birth, but also to delay and activated surfactant related to hyperglycemia and hyperinsulinism. And we can see some of the same hematologic consequences may be related to chronic hypoxia like polycythemia. Um We know quite well about hypoglycemia and transient hypersinus. Um and there's some risk of hypocalcemia as well, which is not fully understood in terms of mechanism, the long term risk, there's actually a risk for the DM baby in developing diabetes um in when they're older. Um and then their neural developmental risk is less clear with the available studies. So some of the take home points here. Um So preconception care is important. Um and we are all a part of it. So um keeping in mind the early timing of organogenesis and the impact on of maternal health conditions on a healthy pregnancy, common pregnancy conditions like hypertension and diabetes are increasing. Many of them, these more common conditions can increase, increase risk for fetal growth restriction and preterm birth, which thereby increases neonatal and childhood complications. And then in addition to significant risk of the pregnancy in the mate fetal growth restriction is correlated with long term health complications like adult metabolic and cardiovascular disease. And um since I have everyone here in this great robust audience and our group that helped me with some of the planning um made me aware of uh one of the new kind of clinics that we have at U CS F. So the Black Baby Equity Clinic Bloom, which was launched just here in July. Um So the that we have the Claremont Clinic which provides um pediatric care. And for this clinic for um any family that identifies as black, they have the option to go to a clinic where they are um served by black providers, which includes um the physicians and also some feeding specialists and support staff. And as we know, there are multiple maternal health disparities faced specifically by black individuals. Um Many of the conditions we talked about today. So I'm very happy to have this clinic. Um And please feel free to speak up. Doctor Ross. I was kind enough to talk with me about this ahead of time. So, thank you all so much. Thank you so much, Doctor Lars. I was really informative. Um Right now would be the time to ask any questions you can either send them to the chat or send them to me privately. I had a couple of questions that were sent in. Um The first question I got was, are there any studies on developmental outcomes comparing those who are born late preterm versus term Children? Um So yes, so sorry. So over a late preterm versus term, yes, late premium versus term. Yes. Um Yeah. And so that was um some of the sides that I had, I won't go back to them. But yes. So um for this area, I find this always challenging because we do counsel a lot of families. So, so yes, there are differences. Um These are not, they're not great differences. So they're not huge in thinking of comparison to our um peri viable babies. So thinking of 23 24 25 leakers, but there is some signal there and there is some increase um in particular in risk of intellectual disability or needing um additional help at school. Um some increased risk. We think of things like a DH D. Um So it's, it's there and it's important to recognize um something that I always talk to families about, particularly in situations where we, we don't have a choice. We, we are facing a preterm delivery is that um knowledge is power and knowing early and being able to intervene early is what can help us offset some of these risks. But yes, that is, that is well studied. And then another question was, what are some of the long term development outcomes of babies who are born with mild ventricular megaly? Yeah, so um so again, thinking of developmental differences. Um and you know, and one thing again, challenging for me when I kind of think of putting myself in, in a parents place is um the, you know, the side I presented, we said, you know, more than 90% will have um will, will not have any impacts on their development. But that means that 10% could. So, um so thinking of um things like intellectual differences, um thinking of physical impairment, cerebral palsy, um particularly being increased in in pregnancies where the fetus was impacted by ventricular megaly. But again, with save for other findings and having good close follow up and seeing resolution um points to a really low risk for any impacts on development and please feel free to reach out. Again, it's always a little bit harder on zoom. So if I'm not answering your question or there's follow up questions, I encourage you to speak up. Next question is um is there any data that prenatal maternal Aceta Finnen is problematic in babies? Oh, that's a good question. Um And this, this is a harder one, this is a newer area and I will apologize in advance because I don't um this, I haven't read so that I can particularly quote you a study. But um but yeah, so as you may be aware in the NICU setting, um we, we think about patent ductus arteriosus and treatment and we have more often used things like ibuprofen or in the mein. Um But more recently, we started using things like acetaminophen which has been helpful and useful. Um So then the question becomes in pregnancy when we want the ductus arteriosus to stay open. Is there um potentially a harmful effect for acetaminophen? Um And if any of my neonatology colleagues are on, please help me to speak up. But my understanding more recently is that there's a signal there. Um And it's something that needs further study. Um but uh that we're not necessarily saying that this absolutely should not be used during pregnancy. Great. And then the next question I got was, what are some of the most common indications for referral to the U CS F Field Treatment Center? And what are some misconceptions on common conditions that do not necessarily always need a referral to the FTC? Hm. Good question. Um So I would say, you know, for us, certainly thinking about um congenital heart disease um that is very helpful to get linked in to actually get a fetal echo done. Um And to be able to work with our cardiology team and with us in terms of where the safest place for delivery would be. Um that's a helpful thing as well. Just in thinking about we um we do our best to, to be aware of what studies and interventions can be done at our many birthing hospitals in the area. And I would say some of the more challenging times would be something like the two topics I pre presented. So we often will see cases of ventricular megaly or hydronephrosis and a lot of the time, you know, patients are being referred over from other MF MS in the area or from the primary obstetricians. And for me, the way I think of it is it is helpful for something like ventricular megaly to have the extra information. So we can provide a fetal MRI which provides much more detailed information in terms of the fetal brain, which can be very helpful. Um Hopefully, if all is is well and looking good in actually preserving the family's birth plan, which would be to allow them to deliver at the the hospital or, or birthing center of their choice. Um in terms of, you know, when we may not need referrals, that's a little bit more challenging. Um You know, I think in terms of the, the early ultrasound at 20 weeks in the level two anatomy scan, um we are, our techniques are getting better and better. So many conditions are being picked up at those scans. Um For some things perhaps like hydronephrosis, it could be followed forward before an automatic referral if there's something like mild or moderate. Um again, not completely my areas, I'm not an obstetrician but um but I think, you know, that I think of it as the conditions where we want to be aware early and start to guide the family where it's helpful to get us involved in the earlier side. We will typically from the neonatology standpoint, wait until further along in the pregnancy to provide a consult. Um Both to allow more information but also um to have a better guidance for the family. Um as they get closer to their delivery date, one guest was hoping that you could go back to the slide on hydronephrosis with the RPD. Sure. And then the next question was, was there any data on any specific risks that African American mothers specifically faced during pregnancy? Um Yes. So, so, um, and actually, well, I'll leave this for now. But, um, but yes, so, so especially the two main conditions like hypertension and diabetes, um can just proportionally impacting um, black mothers. Um And so there's a lot of different factors that go into this and, and um obviously, I would love to have an entire session devoted to it um with more time to prepare. But, and you know, there's concerns about uh less understanding of differences in terms of physiology. There's concerns about um inadequate care or differences in care and a lot of the higher risk related around times of delivery having similar um similar background risk there. So certainly, yes. And, and that's part of the reason I'm very thankful to the group for making me aware of the, the bloom clinic as well. Um and doctor as the embrace clinic as well in, in San Francisco, particularly, you know, putting together um black mothers or black providers to help overcome some of the um the social things that are um contributing to this. Then the next question was, is there any significant risk between maternal use of Tylenol and the later development of autism? It seems that there's been a spike recently in social media discussing this and the question wanted to clarify if there was any causal relationship or not, not that I'm aware of. Um, but that's not something I've gone through the literature on recently. So, I'm, I'm sorry, I'm not able to answer but I'm actually, um, that's, that's good to know. I actually wasn't aware that that was a recent concern that had come up. And can you comment if there's any fetal risk if Zofran is taken early during pregnancy? Yeah. There, there's concern for that. Um I a lot of the studies are, are complicated and as you can imagine, um not a lot of randomized control trials for that as far as I'm aware, um generally, I think it would try to avoid things during organogenesis like I was highlighting earlier on in the talk. Um But certainly that's also the the highest time point where where uh women are facing um nausea and, and differences and um pregnancy health and this one is gonna be a little bit harder for me to answer. So I'm, I'm not not prepared for an eloquent answer on that. And then there is a question about how to refer to Bloom Clinic and where like which babies can be seen at Bloom Clinic. And I'm not actually sure I can answer that question appropriately. I probably would defer to Jave or, or doctor Long, but I know that the clinic is held every Friday from 10 to 2 p.m. And I know that the cho residents can refer or they can place referrals into the Bloom clinic, but I'm not too sure about community pediatricians. Yeah, let's back up. And if anybody is on, please feel free to speak up. Oh, sorry, I missed another question. Um, what is the age of mothers with the most unintended preg, unintended pregnancies? And then is there any plan to increase education of preconception care in school health classes? Especially in states where abortion is now banned? Oh, it's a big one. So I I will have to get back to you in terms of the, the SKU and that was a good reminder because that would be helpful um to have that kind of bar graph in terms of the ages for unintended pregnancy. So I will, I will circle back to the group on that. Um And in terms of of education and, and kind of in school that I am also unsure on. So I do apologize. Um I'm kind of extending my reach here a little bit beyond neonatology. So well, thank you so much, Doctor Larson. If anybody has any questions to ask is the last chance, but it is now nine o'clock. Thanks so much, everyone. Thank you for the very, very good questions you've given me lots to, to think on and circle back to. Created by
