# Presentation: 825576

## Pregnancy Outcome Patterns for Selected Birth Defects in Texas

- Mary Ethen, MPH
- Amy Case, MAHS
- Texas Birth Defects Monitoring Division

## Features of the Texas Birth Defects Registry

- Active surveillance--trained staff visit facilities to collect information
- Coverage of more than 365,000 live births annually (statewide)
- Computerized database of infants and pregnancies affected by birth defects
- Emphasis on structural malformations
- Cases matched to vital record

## Texas Birth Defects Registry Case Definition

- Mother resides in Texas at delivery
- Includes live births, fetal deaths, and elective terminations of any gestational age
- Infant/fetus must have one or more structural or chromosomal birth defects, or Fetal Alcohol Syndrome
- Defect must be diagnosed within the first year after delivery (within six years for Fetal Alcohol Syndrome)

**Notes:**

Notes:

## Methods

- Deliveries in the Texas Birth Defects Registry that occurred 1999-2000
- Forty-nine major defect categories
- Gestational age calculated from last menstrual period (LMP) or neonatal examination

**Notes:**
49 categories reflect national conventions for reporting of birth defects
64%of all 1999-2000 Cases in the Registry have one or more of the 49 defects covered in this analysis
Therefore, 36% of cases in the Registry for this time period are not included in this study
Babies will often have more than one defect—these data were analyzed regardless of the occurrence of other defects.  Not limited to isolated defects. 
Calculating gestational age:
Used GA by LMP if 8-44 weeks
Otherwise, used GA by neonatal exam

## Methods

- Pregnancy outcome based on information abstracted from medical records
- Registry records matched to vital records
- 97% agreement between pregnancy outcome (Registry) and type of vital record matched

**Notes:**
Live birth matched to birth certificate.
Fetal death (>20 weeks) matched to fetal death certificate
Agreement for elective terminations = no certificate of either kind.

Matched by names, child’s DOB, Mother’s DOB, etc.

## Live Birth

- Complete expulsion or extraction a product of conception
- Any gestational age
- After delivery, shows any vital signs (heartbeat, voluntary breathing, umbilical cord pulsation, voluntary muscle movement)
- Most common outcome by far of Registry cases

- 100% of Cases in Registry were Live Birth for these Defects:
- Cataract
- Aniridia
- Hirschsprung Disease
- Biliary Atresia
- Bladder Exstrophy
- Congenital Hip Dislocation
- FAS

**Notes:**
Our ascertainment for live births is probably much more complete for live births, which may influence the extremely high proportion of live births in our data.

## Fetal Death

**Spontaneous death of a product of conception prior to the complete expulsion or extraction from its mother.**
**Onset of labor may be natural or induced.**
**Also referred to as spontaneous abortion, miscarriage or stillbirth.**
**Outcome in 1.83% of Texas infants and fetuses with a birth defect.**

**Examples (any gestational age):**
**Anencephaly (21.7%)**
**Holoprosencephaly (10.5%)**
**Anophthalmia (14.3%)**
**Lower Limb Reduction (10.5%)**
**Omphalocele (12.0%)**
**Trisomy 13 (10.5%)**
**Trisomy 18 (11.6%)**

**Notes:**
The spontaneous death of a product of conception prior to the complete expulsion or extraction from its mother, regardless of the length of gestation. The onset of labor may be natural or
induced. Spontaneous fetal deaths may also be referred to as spontaneous abortions or miscarriages (both usually referring to fetal deaths at less than 20 weeks gestation), or as stillbirths (usually referring to fetal deaths at 20 or more weeks gestation).
Holoprosencephaly  Failure of the brain to develop into two equal halves, so there is structural abnormality of the brain.  There may be associated midline facial defects including cyclopia (fusion of the eye orbits into a single cavity containing one eye) in severe cases. About half the cases are probably due to a single gene defect (the HPE gene). Frequently occurs with Trisomy 13.
Anopthalmia  A developmental defect characterized by complete absence of the eyes, or by the presence of vestigial eyes.
Reduction defects of the lower limbs  The congenital absence of a portion of the lower limb.  There are two general types of defect, transverse and longitudinal.  Transverse defects appear like amputations, or like missing segments of the limb.  Longitudinal defects are missing rays of the limb (for example,  a missing tibia and great toe).
Omphalocele  The protrusion of an organ into the umbilicus.  The defect is usually closed surgically soon after birth. Contrast with Gastroschisis.
Patau syndrome (Trisomy 13)  The chromosomal abnormality caused by a extra chromosome 13.  The extra copy can be free‐lying, or can be attached to some other chromosome. Patau syndrome can occur in  mosaic so that there is a population of normal cells and a population of trisomy 13 cells. Patau syndrome is characterized by impaired midline facial development, cleft lip and palate, polydactyly and mental retardation.  Most infants do not survive beyond 6 months of life.
Edwards syndrome (Trisomy 18)  The chromosomal abnormality characterized by an extra copy of chromosome 18.  The extra chromosome can be free lying or attached to another chromosome.  Trisomy 18 can occur in mosaic. Edwards syndrome is characterized by mental retardation, neonatal hepatitis, low‐set ears, skull malformation and short digits.  Cardiac and renal anomalies are also common.  Survival for more than a few months is rare.

## Induced Termination

**After pregnancy is medically verified**
**Intended to terminate intrauterine pregnancy (other than for the purpose of either the birth of a live infant or the removal of a dead fetus)  **
**Also referred to as **
**induced abortion**
**therapeutic abortion**
**elective abortion**
**elective termination**
**Outcome in 2.32% of Texas infants and fetuses with a birth defect**

**Examples (any gestational age):**
**Anencephaly (48.9%)**
**Encephalocele (28.6%)**
**Holoprosencephaly (17.11%)**
**Anophthalmia (33.3%)**
**Omphalocele (16.4%)**
**Trisomy 13 (24.2%)**
**Trisomy 18 (40.7%)**

**Notes:**
Certain conditions frequently result in elective pregnancy terminations.  In general, the conditions with a high occurrence of elective terminations include those which are amenable to prenatal diagnosis and which have poor prognoses for survival. 
Encephalocele  The protrusion of the brain substance through a defect in the skull.
Holoprosencephaly  Failure of the brain to develop into two equal halves, so there is structural abnormality of the brain.  There may be associated midline facial defects including cyclopia (fusion of the eye orbits into a single cavity containing one eye) in severe cases. About half the cases are probably due to a single gene defect (the HPE gene). Frequently occurs with Trisomy 13.
Anopthalmia  A developmental defect characterized by complete absence of the eyes, or by the presence of vestigial eyes.
Omphalocele  The protrusion of an organ into the umbilicus.  The defect is usually closed surgically soon after birth. Contrast with Gastroschisis.

## Pregnancy Outcome & Gestational Age Categories

**Live Birth, Any Gestational Age**
**Fetal Death <20 Weeks Gestation**
**Fetal Death 20+ Weeks Gestation**

**Induced Termination, <20 Weeks Gestation**
**Induced Termination, 20+ Weeks Gestation**
**Unspecified fetal death or medical termination**

**Notes:**
Why we broke Fetal Death and Induced Termination by <20 weeks gestation and 20+:
Convention
Make it possible to compare to registries that only collect 20+
Some state vitals stats offices only require fetal death registration at 20+

## Factors that May Influence Pregnancy Outcome

**Mother’s health (infections, treatment for chronic conditions) **
**Prenatal diagnosis**
**Prognosis for Child**
**Lethality of defect**
**Degree of impairment**
**Expectation of health**
**Co-occurring defects**

**Others?**
**__________________________**
**__________________________**
**__________________________**

**Notes:**
We did not control for these factors in our analysis.

## Infants and Fetuses with Any Monitored Defect

**GA = Gestational Age**

**Notes:**
The vast majority of the cases in our registry result in live births.  Varies by type of defect.

## Pregnancy Outcomes for Selected Neural Tube DefectsTexas, 1999-2000

**Notes:**
Neural tube defects (NTDs) are a group of birth defects presumed to have a common origin in failure of the neural tube to develop properly during the embryonic stage.  NTDs are comprised mainly of anencephaly (including craniorachischisis), spina bifida (including meningo­myelocele, meningocele, and myelocele), and encephalocele.  Anencephaly involves absence of the skull, with the cerebral hemispheres completely missing or reduced to small masses attached to the base of the skull.  Spina bifida is defective closure of the bony encasement of the spinal cord, through which the cord and meninges may or may not protrude. Encephalocele is protrusion of some or all of the brain through a defect in the skull.

## Pregnancy Outcomes for Selected Chromosomal Defects (Trisomies), Texas, 1999-2000

**Notes:**
Down syndrome (trisomy 21)
most common autosomal abnormality among live births
caused by an extra copy of chromosome 21
associated with a variety of structural malformations particularly cardiac malformations.  

Patau syndrome (trisomy 13)
extra copy of chromosome 13
characterized by impaired midline facial development, cleft lip and palate, polydactyly, and mental retardation
If live born, rarely survive beyond 6 months of life

Edwards syndrome (trisomy 18)
extra copy of chromosome 18
characterized by mental retardation, neonatal hepatitis, low-set ears, skull malformation, and short digits; cardiac and renal anomalies are also common. 
Survival of more than a few months is rare

The patterns of pregnancy outcomes for these three trisomies differ from each other, and from the analysis we did in 1996-1997.  Among the three trisomies, Down syndrome is the most likely to result in a live birth, and the least likely to result in a fetal death or an elective termination.  Patau syndrome is the least likely of the trisomies to result in a live birth, and the most likely to result in a fetal death or elective termination.  The distribution of pregnancy outcomes for Edwards syndrome is in between those for Down syndrome and for Patau syndrome. 

## Pregnancy Outcomes for Selected Abdominal Wall DefectsTexas, 1999-2000

**Notes:**
Omphalocele is an abdominal wall defect involving herniation of the bowel and liver into the umbilical cord.  The defect is always covered by a membrane, although some­times this membrane may rupture, in which case the defect may be mistaken for gastroschisis.  Infants with omphalocele tend to have more additional birth defects, including chromosomal abnormalities (most often trisomy 13, trisomy 18, and trisomy 21), and a lower survival rate than infants with gastroschisis.  
Gastroschisis is an abdominal wall defect involving herniation of the intestines and sometimes the liver outside of the abdomen.  The defect occurs lateral to the umbilicus, usually on the right, and never includes a covering sac.  The defect may be confused with other abdominal wall defects such as omphalocele and body stalk anomaly.  Infants with gastroschisis tend to have fewer additional birth defects, including chromosomal abnormalities, and a higher survival rate than infants with other abdominal wall defects, particularly omphalocele.  

The pregnancy outcome patterns for omphalocele and gastroschisis are very different. Omphalocele is much less likely to result in a live birth, and much more likely to result in a fetal death or elective termination, than gastroschisis. 

## Pregnancy Outcomes for Selected Defects, Texas, 1999-2000

**Notes:**
These groups encompass a great range of severity.  The more severe forms are highly associted with each other.  Non-functioning fetal kidneys invariably leads to inadequate lung development.

Renal agenesis or dysgenesis includes the absence of one or both of the kidneys or a deviation in the embryonic development of the kidney.  Unilateral renal agenesis may be asymptomatic and is often incidentally diagnosed by abdominal ultrasound or computed tomography (CT) scan secondary to another condition.  Bilateral renal agenesis is invariably fatal.  

Agenesis, aplasia, or hypoplasia of the lung includes the absence or incomplete development of the lung or lung tissue.  When bilateral renal agenesis occurs, hypoplasia of the lung is almost always a co-occurring condition.  
Examination of these two groups revealed that 20.8% of the cases with a diagnosis in the category renal agenesis/dysgenesis also had agenesis, aplasia, or hypoplasia of the lung, and 22.6% of the cases with agenesis, aplasia, or hypoplasia of the lung also had renal agenesis/dysgenesis.  While there is a fair amount of overlap between these two groups, the co-occurrence of these defects cannot completely account for the striking similarity in pregnancy outcome patterns for these two defects. 

Renal agenesis or dysgenesis cases that also have Agenesis, aplasia or hypoplasia of the lung = 76/366 =20.77%
Agenesis, aplasia or hypoplasia of the lung cases that also have Renal agenesis or dysgenesis = 76/337 =22.55%

Renal agenesis or dysgenesis  The failure, or deviation, of embryonic development of the kidney.
Agenesis, aplasia, or hypoplasia of the lung  The absence or incomplete development of a lung or lung tissue. 

## Reduction Defects of the Lower Limbs

**Notes:**
Missing lower limbs are associated with monozygotic twining—could explain relatively high rate of fetal death.
According to Smith’s “there appears to be an increased likelihood of fetal death in one or more of MZ twins who develop in a monoamnionic sac”

## Pregnancy Outcome Other than Live Birth, by Maternal Race/Ethnicity

**Notes:**
Overall data do not indicate 

## Percent of Cases Resulting in Induced Termination by Maternal Race/Ethnicity

## Percent of Cases Resulting in Fetal Death by Maternal Race/Ethnicity

**Notes:**
Cleft lip  The congenital failure of the fetal components of the lip to fuse or join, forming a groove or fissure in the lip.  Infants with this condition can have difficulty feeding, and may use assistive devices for feeding.  This condition is corrected when the infant can tolerate surgery.  
Cleft palate   The congenital failure of the palate to fuse properly, forming a grooved depression or fissure in the roof of the mouth.  This defect varies in degree of severity. The fissure can extend into the hard and soft palate and into the nasal cavities.  Infants with this condition have difficulty feeding, and may use assistive devices for feeding. Surgical correction is begun as soon as possible. Children with cleft palates are at high risk for hearing problems due to ear infections.

## Limitations

- Possible misclassification of pregnancy outcomes
- Difficult to determine intended outcome from medical record
- Lethal/non-lethal conditions in the same defect group (e.g. renal agenesis/ dysgenesis)

- Birth defects among early fetal deaths (miscarriage) and early terminations likely to be under-ascertained
- Less severe defects co-occur with more severe defects
- Analysis not restricted to isolated defects

## Acknowledgements

- TBDMD Surveillance Staff
- Texas Department of Health Bureau of Vital Statistics
- Mark Canfield, Ph.D., Director, Texas Birth Defects Monitoring Division